Metabolic Fingerprint of Acromegaly and its Potential Usefulness in Clinical Practice.

Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels are the main targets for monitoring acromegaly activity, but they are not in close relationship with the clinical course of the disease and the associated comorbidities. The present study was aimed at identifying metabolites that could be used as biomarkers for a better disease phenotyping. For this purpose, metabolic fingerprint using an untargeted metabolomic approach was examined in serum from 30 patients with acromegaly and 30 age-matched controls. Patients with acromegaly presented fewer branched-chain amino acids (BCAAs) compared to the control group (valine: 4.75 ± 0.87 vs. 5.20 ± 1.06 arbitrary units (AUs), p < 0.05; isoleucine: 2.54 ± 0.41 vs. 2.80 ± 0.51 AUs; p < 0.05). BCAAs were also lower in patients with active disease compared to patients with normal levels of IGF-1 with or without medical treatment. GH, but not IGF-1, serum levels were inversely correlated with both valine and isoleucine. These findings indicate that low levels of BCAAs represent the main metabolic fingerprint of acromegaly and that GH, rather than IGF-1, might be the primary mediator. In addition, our results suggest that the assessment of BCAAs could help to identify active disease and to monitor the response to therapeutic strategies.

MEN1-associated primary hyperparathyroidism in the Spanish Registry: clinical characterictics and surgical outcomes.

Primary hyperparathyroidism is the most frequent manifestation of multiple endocrine neoplasia type 1 (MEN1) syndrome. Bone and renal complications are common. Surgery is the treatment of choice, but the best timing for surgery is controversial and predictors of persistence and recurrence are not well known. Our study describes the clinical characteristics and the surgical outcomes, after surgery and in the long term, of the patients with MEN1 and primary hyperparathyroidism included in the Spanish Registry of Multiple Endocrine Neoplasia, Pheochromocytomas and Paragangliomas (REGMEN). Eighty-nine patients (49 men and 40 women, 34.2 ± 13 years old) were included. Sixty-four out of the 89 underwent surgery: a total parathyroidectomy was done in 13 patients, a subtotal parathyroidectomy in 34 and a less than subtotal parathyroidectomy in 15. Remission rates were higher after a total or a subtotal parathyroidectomy than after a less than subtotal (3/4 and 20/22 vs 7/12, P < 0.05), without significant differences in permanent hypoparathyroidism (1/5, 9/23 and 0/11, N.S.). After a median follow-up of 111 months, 20 of the 41 operated patients with long-term follow-up had persistent or recurrent hyperparathyroidism. We did not find differences in disease-free survival rates between different techniques, patients with or without permanent hypoparathyroidism and patients with different mutated exons, but a second surgery was more frequent after a less than subtotal parathyroidectomy.

Genetic Testing to Predict Weight Loss and Diabetes Remission and Long-Term Sustainability after Bariatric Surgery: A Pilot Study.

INTRODUCTION: The aim of this pilot study was to assess genetic predisposition risk scores (GPS) in type 2 diabetic and non-diabetic patients in order to predict the better response to bariatric surgery (BS) in terms of either weight loss or diabetes remission. RESEARCH DESIGN AND METHODS: A case-control study in which 96 females (47 with type 2 diabetes) underwent Roux-en-Y gastric by-pass were included. The DNA was extracted from saliva samples and SNPs were examined and grouped into 3 GPS. ROC curves were used to calculate sensitivity and specificity. RESULTS: A highly sensitive and specific predictive model of response to BS was obtained by combining the GPS in non-diabetic subjects. This combination was different in diabetic subjects and highly predictive of diabetes remission. Additionally, the model was able to predict the weight regain and type 2 diabetes relapse after 5 years' follow-up. CONCLUSIONS: Genetic testing is a simple, reliable and useful tool for implementing personalized medicine in type 2 diabetic patients requiring BS.

Estudio Longitudinal de Crecimiento Barcelona 1995-2017 / Barcelona Longitudinal Growth Study 1995-2017

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Pasireótida en acromegalia por tumores agresivos, descripción de 4 casos. Hacia una medicina personalizada / Pasireotide in acromegaly by aggressive tumors, description of four clinical cases. Towards a personalized medicine

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Response to oral sucrosomial iron supplementation in patients undergoing bariatric surgery. The BARI-FER study / Respuesta a la suplementación oral con hierro sucrosomado en pacientes sometidos a cirugía bariátrica. Estudio BARI-FER

Background: Chronic intravenous iron administration is often required after bariatric surgery. Oral sucrosomial iron has a particular form of absorption and may represent an alternative treatment. Objective: To assess the effect of switching to oral sucrosomial iron in patients receiving intravenous iron supplementation after bariatric surgery. Patients and methods: A case-control study was conducted on 40 women of childbearing age, of whom 20 were switched to oral sucrosomial iron, while 20 patients continued on intravenous iron sucrose every three months. Results: No significant differences were seen in Hb, ferritin, and TSI levels before and after three months of treatment with sucrosomial iron. Conclusion: Oral sucrosomial iron could be an alternative in patients who require parenteral treatment with iron after bariatric surgery (AU)

Antecedentes: A menudo es necesaria la administración intravenosa crónica de hierro después de la cirugía bariátrica. El hierro sucrosomado oral tiene una forma especial de absorción y es un posible tratamiento alternativo. Objetivo: Valorar el efecto del cambio al hierro sucrosomado oral en los pacientes que reciben suplementos de hierro por vía intravenosa después de cirugía bariátrica. Pacientes y métodos: Se realizó un estudio de casos y controles que incluyó a 40 mujeres en edad fértil, de la que 20 se cambiaron a hierro sucrosomado oral, mientras que las 20 restantes siguieron recibiendo hierro sacarosa cada tres meses. Resultados: No se observaron diferencias importantes en los niveles de Hb, ferritina ni TSI hallados antes y después de tres meses de tratamiento con hierro sucrosomado. Conclusión: El hierro sucrosomado oral puede ser una alternativa en los pacientes que necesitan tratamiento parenteral con hierro después de cirugía bariátrica (AU)

Response to oral sucrosomial iron supplementation in patients undergoing bariatric surgery. The BARI-FER study.

BACKGROUND: Chronic intravenous iron administration is often required after bariatric surgery. Oral sucrosomial iron has a particular form of absorption and may represent an alternative treatment. OBJECTIVE: To assess the effect of switching to oral sucrosomial iron in patients receiving intravenous iron supplementation after bariatric surgery. PATIENTS AND METHODS: A case-control study was conducted on 40 women of childbearing age, of whom 20 were switched to oral sucrosomial iron, while 20 patients continued on intravenous iron sucrose every three months. RESULTS: No significant differences were seen in Hb, ferritin, and TSI levels before and after three months of treatment with sucrosomial iron. CONCLUSION: Oral sucrosomial iron could be an alternative in patients who require parenteral treatment with iron after bariatric surgery.

Biopsia selectiva del ganglio centinela en el carcinoma papilar de tiroides en pacientes sin evidencia preoperatoria de metástasis ganglionar / Selective sentinel lymph node biopsy in papillary thyroid carcinoma in patients with no preoperative evidence of lymph node metastasis

Introducción: La linfadenectomía en la cirugía del carcinoma papilar de tiroides se aconseja cuando hay evidencia de metástasis ganglionar cervical (terapéutica) o en pacientes de alto riesgo (profiláctica), como en los tumores T3 y T4 de la clasificación TNM. La técnica de la biopsia selectiva del ganglio centinela puede mejorar el diagnóstico prequirúrgico de las metástasis ganglionares. Objetivo: Analizar el resultado de la biopsia selectiva del ganglio centinela en un grupo de pacientes con carcinoma papilar de tiroides T sin evidencia de afectación ganglionar antes de la cirugía. Pacientes y método: Estudio retrospectivo, unicéntrico en el que se incluyeron los pacientes intervenidos entre los años 2011-2013 que fueran clínicamente N0. La identificación del ganglio centinela se realizó mediante técnica isotópica. En todos los casos, se practicó linfadenectomía del compartimento afecto si el ganglio centinela era positivo, y del compartimento central en caso de ganglio centinela negativo. Resultados: Se incluyeron 43 pacientes, 34 mujeres, con una edad media de 52,3 (±17) años. De los 170 ganglios centinela resecados, 46 (27%) fueron positivos para metástasis, que correspondían a 24 (55,8%) pacientes. En las linfadenectomías se resecaron 612 ganglios. De ellos, 96 (15,6%) fueron positivos para metástasis. Doce de los treinta (40%) pacientes cT1N0 y cT2N0 pasaron a pN1 tras la biopsia selectiva del ganglio centinela, mientras que 12 de los 13 (92%) pacientes cT3N0 y cT4N0, acabaron siendo pN1. Conclusiones: La biopsia selectiva del ganglio centinela recalifica más del 50% de pacientes de cN0 a pN1. Se confirma la necesidad de vaciamiento ganglionar en los tumores T3 y T4, pero pone al descubierto la presencia de metástasis linfáticas en el 40% de los T1-T2 (AU)

Introduction: Lymphadenectomy is recommended during surgery for papillary thyroid carcinoma when there is evidence of cervical lymph node metastasis (therapeutic) or in high-risk patients (prophylactic) such as those with T3 and T4 tumors of the TNM classification. Selective sentinel lymph node biopsy may improve preoperative diagnosis of nodal metastases. Objective: To analyze the results of selective sentinel lymph node biopsy in a group of patients with papillary thyroid carcinoma and no evidence of nodal involvement before surgery. Patients and method: A retrospective, single-center study in patients with papillary thyroid carcinoma and no clinical evidence of lymph node involvement who underwent surgery between 2011 and 2013. The sentinel node was identified by scintigraphy. When the sentinel node was positive, the affected compartment was removed, and when sentinel node was negative, central lymph node dissection was performed. Results: Forty-three patients, 34 females, with a mean age of 52.3 (±17) years, were enrolled. Forty-six (27%) of the 170 SNs resected from 24 (55.8%) patients were positive for metastasis. In addition, 94 (15.6%) out of the 612 lymph nodes removed in the lymphadenectomies were positive for metastases. Twelve of the 30 (40%) low risk patients (cT1N0 and cT2N0) changed their stage to pN1, whereas 12 of 13 (92%) high risk patients (cT3N0 and cT4N0) changed to pN1 stage. Conclusions: Selective sentinel lymph node biopsy changes the stage of more than 50% of patients from cN0 to pN1. This confirms the need for lymph node resection in T3 and T4 tumors, but reveals the presence of lymph node metastases in 40% of T1-T2 tumors (AU)

Selective sentinel lymph node biopsy in papillary thyroid carcinoma in patients with no preoperative evidence of lymph node metastasis. / Biopsia selectiva del ganglio centinela en el carcinoma papilar de tiroides en pacientes sin evidencia preoperatoria de metástasis ganglionar.

INTRODUCTION: Lymphadenectomy is recommended during surgery for papillary thyroid carcinoma when there is evidence of cervical lymph node metastasis (therapeutic) or in high-risk patients (prophylactic) such as those with T3 and T4 tumors of the TNM classification. Selective sentinel lymph node biopsy may improve preoperative diagnosis of nodal metastases. OBJECTIVE: To analyze the results of selective sentinel lymph node biopsy in a group of patients with papillary thyroid carcinoma and no evidence of nodal involvement before surgery. PATIENTS AND METHOD: A retrospective, single-center study in patients with papillary thyroid carcinoma and no clinical evidence of lymph node involvement who underwent surgery between 2011 and 2013. The sentinel node was identified by scintigraphy. When the sentinel node was positive, the affected compartment was removed, and when sentinel node was negative, central lymph node dissection was performed. RESULTS: Forty-three patients, 34 females, with a mean age of 52.3 (±17) years, were enrolled. Forty-six (27%) of the 170 SNs resected from 24 (55.8%) patients were positive for metastasis. In addition, 94 (15.6%) out of the 612 lymph nodes removed in the lymphadenectomies were positive for metastases. Twelve of the 30 (40%) low risk patients (cT1N0 and cT2N0) changed their stage to pN1, whereas 12 of 13 (92%) high risk patients (cT3N0 and cT4N0) changed to pN1 stage. CONCLUSIONS: Selective sentinel lymph node biopsy changes the stage of more than 50% of patients from cN0 to pN1. This confirms the need for lymph node resection in T3 and T4 tumors, but reveals the presence of lymph node metastases in 40% of T1-T2 tumors.

Ectopic Cushing's syndrome: Paradoxical effect of somatostatin analogs / Secreción ectópica de ACTH y respuesta paradójica a análogos de somatostatina

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Brown tumor of the jaw after pregnancy and lactation in a MEN1 patient.

Skeletal manifestations of primary hyperparathyroidism (pHPT) include brown tumors (BT), which are osteoclastic focal lesions often localized in the jaws. Brown tumors are a rare manifestation of pHTP in Europe and USA; however, they are frequent in developing countries, probably related to vitamin D deficiency and longer duration and severity of disease. In the majority of cases, the removal of the parathyroid adenoma is enough for the bone to remineralize, but other cases require surgery. Hyperparathyroidism in MEN1 develops early, and is multiglandular and the timing of surgery remains questionable. To our knowledge, there are no reports of BT in MEN 1 patients. We present a 29-year-old woman with MEN 1 who developed a brown tumor of the jaw 24 months after getting pregnant, while breastfeeding. Serum corrected calcium remained under 2.7 during gestation, and at that point reached a maximum of 2.82 mmol/L. Concomitant PTH was 196 pg/mL, vitamin D 13.7 ng/mL and alkaline phosphatase 150 IU/L. Bone mineral density showed osteopenia on spine and femoral neck (both T-scores = -1.6). Total parathyroidectomy was performed within two weeks, with a failed glandular graft autotransplantation, leading to permanent hypoparathyroidism. Two months after removal of parathyroid glands, the jaw tumor did not shrink; thus, finally it was successfully excised. We hypothesize that higher vitamin D and mineral requirements during maternity may have triggered an accelerated bone resorption followed by appearance of the jaw BT. We suggest to treat pHPT before planning a pregnancy in MEN1 women or otherwise supplement with vitamin D, although this approach may precipitate severe hypercalcemia. LEARNING POINTS: Brown tumors of the jaw can develop in MEN 1 patients with primary hyperparathyroidism at a young age (less than 30 years).Pregnancy and lactation might trigger brown tumors by increasing mineral and vitamin D requirements.Early parathyroidectomy is advisable in MEN 1 patients with primary hyperparathyroidism, at least before planning a pregnancy.Standard bone mineral density does not correlate with the risk of appearance of a brown tumor.Removal of parathyroid glands does not always lead to the shrinkage of the brown tumor, and surgical excision may be necessary.

Nuevos hipoglucemiantes orales y riesgo cardiovascular. Cruzando la frontera metabólica / New oral hypoglycemic agents and cardiovascular risk. crossing the metabolic border

Los inhibidores del cotransportador de sodio-glucosa tipo 2 son una nueva clase de hipoglucemiantes orales que aumentan de la excreción urinaria de glucosa independientemente de la secreción de insulina. Sin embargo, este mecanismo aparentemente sencillo conduce a efectos metabólicos indirectos más complejos. Los resultados clínicos demuestran su efectividad en el control de la glucemia, pues reducen la glucohemoglobina y, al mismo tiempo, logran una disminución del peso corporal y de la presión arterial sistólica. Esta revisión proporciona una visión general de la evidencia disponible hasta el momento sobre el mecanismo de acción, la eficacia y la seguridad, así como otros factores de riesgo más allá de la glucosa que se podría modular de manera positiva con los fármacos comercializados actualmente. Datos recientes sobre la empagliflozina que muestran un beneficio cardiovascular específico obligan a actualizar el conocimiento de esta nueva clase terapéutica para el tratamiento de la diabetes mellitus tipo 2 (AU)

Sodium-glucose cotransporter 2 inhibitors are a novel pharmacological class of oral hypoglycemic agents that lower glucose levels by increasing renal glucose excretion in an insulin-independent manner. However, this seemingly simple mechanism has more complex indirect metabolic effects. The results of randomized clinical trials have shown that these inhibitors effectively lower blood glucose and glycated hemoglobin levels without increasing the risk of hypoglycemia and, at the same time, also reduce bodyweight and systolic blood pressure. In this review, we describe the mechanism of action, efficacy, and safety of currently marketed drugs, as well as other risk factors besides glucose that can potentially be modulated positively. Recent data on empagliflozin showing a significant cardiovascular benefit have compelled us to update knowledge of this new therapeutic class for the treatment of type 2 diabetes (AU)

New Oral Hypoglycemic Agents and Cardiovascular Risk. Crossing the Metabolic Border.

Sodium-glucose cotransporter 2 inhibitors are a novel pharmacological class of oral hypoglycemic agents that lower glucose levels by increasing renal glucose excretion in an insulin-independent manner. However, this seemingly simple mechanism has more complex indirect metabolic effects. The results of randomized clinical trials have shown that these inhibitors effectively lower blood glucose and glycated hemoglobin levels without increasing the risk of hypoglycemia and, at the same time, also reduce bodyweight and systolic blood pressure. In this review, we describe the mechanism of action, efficacy, and safety of currently marketed drugs, as well as other risk factors besides glucose that can potentially be modulated positively. Recent data on empagliflozin showing a significant cardiovascular benefit have compelled us to update knowledge of this new therapeutic class for the treatment of type 2 diabetes.

Eliminación renal de glucosa como tratamiento de la diabetes: de un antiguo método diagnóstico a una nueva forma de tratamiento / Glucose renal excretion as diabetes treatment: from an old diagnostic method to a new way of treatment

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Dos décadas de tratamiento con hormona de crecimiento en la edad adulta / Two decades of growth hormone treatment in adulthood

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Immunohistochemical Expression of Estrogen Receptor-α and Progesterone Receptor in Patients with Papillary Thyroid Cancer.

BACKGROUND: Papillary thyroid cancer (PTC) prevalence is nearly 3 times higher in females than in males. This gender difference suggests that growth and progression of PTC might be influenced by female sex hormones. OBJECTIVES: To analyze the expression of both estrogen receptor (ER)-α and progesterone receptor (PR) by immunohistochemistry in 203 PTC patients. METHODS: ER-α and PR expression was evaluated in paraffin-embedded tumor tissue samples of 45 males and 158 females followed up for 7.2 ± 3.7 years. RESULTS: ER-α was expressed in 52 (25.6%) patients (41 females and 11 males) and PR in 94 (46.3%) patients (75 females and 19 males). ER-α and PR were coexpressed in 31 (15.3%) patients (27 females and 4 males). ER-α expression correlated significantly with tumor size in the whole sample (ER-α positive 22.8 ± 11.8 mm vs. ER-α negative 15.1 ± 12.4 mm; p = 0.02) and in the subgroup of women (ER-α positive 18.8 ± 12.8 mm vs. ER-α negative 14.9 ± 12.3 mm; p = 0.048). In addition, ER-α expression significantly correlated with remission of the disease. In fact, of the 192 patients followed up, 50/153 (32.7%) disease-free patients were ER-α positive, in contrast to only 3/39 (7.7%) with evidence of disease persistence/recurrence (χ2 = 8.5, p = 0.0036). PR expression was not associated with any of the parameters analyzed. CONCLUSIONS: The present study confirmed recent data indicating that ER-α and PR expression is a common finding in thyroid tumor tissue. However, in contrast to previous reports, we observed an association between ER-α expression and a more favorable outcome in PTC patients.