Bone mineral density in familial partial lipodystrophy.

OBJECTIVE: Type 1 and type 2 familial partial lipodystrophies (FPLD) are characterized by the loss or increase in subcutaneous fat in certain body regions, as well as metabolic disorders. Higher muscle volume and mass have also been described. However, so far, possible bone involvement has not been studied. The aim of this study was to evaluate bone mineral density (BMD) in patients with type 1 and type 2 FPLD. METHODS: A total of 143 women were selected and distributed into three groups (17 women with FPLD2, 82 women with FPLD1 and 44 nonlipodystrophic obese female controls). A thorough history and physical examination were carried out on all subjects, as well as the measurement of anthropometric features. BMD along with fat and fat-free mass (FFM) were determined by DXA (dual-energy X-ray absorptiometry). Statistical analyses, primarily using the χ2 , ANOVA and ANCOVA tests, were performed, using age, height, fat and FFM as covariables. RESULTS: After eliminating the possible influences of age, height, fat and FFM, we observed that there were no significant differences in total BMD between patients with FPLD and the control group, showing total BMD values of 1.092 ± 0.037 g/cm2 in the FPLD2 group, 1.158 ± 0.013 g/cm2 in the FPLD1 group and 1.173 ± 0.018 g/cm2 in the control group (P = .194). Similarly, no significant differences were found in segmental BMD. CONCLUSIONS: Unlike in other types of laminopathy in which bone is affected, in the case of FPLD, there are no differences in BMD compared to nonlipodystrophic subjects.

[Immunonutrition, evidence and experiences]. / Inmunonutrición, evidencias y experiencias.

Introduction: Immunonutrition is a science that encompasses aspects related to nutrition, immunity, infection, inflammation and tissue damage. Immunomodulatory formulas have shown benefits in a wide variety of clinical situations. The objective of this work was to review the available evidence in immunonutrition (IN). For this, a bibliographic search has been carried out with the keywords: immunonutrition, arginine, glutamine, nucleotides, omega-3 fatty acids, ERAS, fast-track. Clinical trials, reviews and clinical practice guidelines have been included. IN has been shown to reduce postoperative fistulae in head and neck cancer patients and in gastric and esophageal cancer patients, infectious complications and hospital stay. Other clinical situations that benefit from the use of IN are pancreatic cancer surgery, colorectal cancer surgery and major burns. More controlled, prospective, and randomized studies are necessary to confirm the potential benefits of IN in other clinical situations such as non-esophageal thoracic surgery, bladder cancer, gynecological surgery, hip fracture, liver pathology and COVID-19, among others.

Introducción: La inmunonutrición es una ciencia que engloba aspectos relacionados con la nutrición, la inmunidad, la infección, la inflamación y el daño tisular. Las fórmulas inmunomoduladoras han demostrado beneficios en una amplia variedad de situaciones clínicas. El objetivo de este trabajo es revisar la evidencia disponible en inmunonutrición (IN). Para ello, se ha realizado una búsqueda bibliográfica con las palabras clave: inmunonutrición, arginina, glutamina, nucleótidos, ácidos grasos omega-3, ERAS, fast-track. Se han incluido ensayos clínicos, revisiones y guías de práctica clínica. La IN ha demostrado reducir las fístulas en el postoperatorio en pacientes con cáncer de cabeza y cuello. En pacientes con cáncer gástrico y cáncer de esófago, la IN se asocia a una disminución de las complicaciones infecciosas y la estancia hospitalaria. Otras situaciones clínicas que se benefician del uso de la IN son la cirugía del cáncer de páncreas, la cirugía del cáncer colorrectal y los grandes quemados. Son necesarios más estudios controlados, prospectivos y aleatorizados para confirmar los potenciales beneficios de la IN en otras situaciones clínicas como la cirugía torácica no esofágica, el cáncer vesical, la cirugía ginecológica, la fractura de cadera, la patología hepática y la COVID-19, entre otros.

[Severe hypocupremia and familial amyloid polyneuropathy]. / Hipocupremia severa y polineuropatía amiloidótica familiar por transtiretina.

INTRODUCTION: Introduction: we report a patient with transthyretin familial amyloid polyneuropathy (TTR-FAP) and severe hypocupremia. Case report: a 79-year-old male with TTR-FAP and severe malnutrition. Laboratory tests showed low serum copper (Cu) and ceruloplasmin levels, as well as low urinary Cu levels. The patient reported neither digestive symptoms nor previous gastrointestinal surgery. Liver function tests, iron metabolism, hemoglobin, leukocytes and zinc were normal. Discussion: Cu is a trace element. It is part of the cuproenzymes involved in several physiological functions. Hypocupremia can be related to genetic or acquired etiologies, including low intake, bariatric surgery, increased losses, etc. Primary clinical manifestations include hematological (anemia and leukopenia) and neurological (myelopathy, peripheral neuropathy) features. Treatment is empirical. In severe cases it may be initiated with endovenose administration, followed by oral supplementation.

INTRODUCCIÓN: Introducción: presentamos el caso de un paciente con antecedentes de polineuropatía amiloidótica familiar por transtiretina (TTR-FAP) diagnosticado de hipocupremia severa. Caso clínico: varón de 79 años afecto de TTR-FAP. Visto en consulta de nutrición por desnutrición severa. En el estudio analítico presenta cifras de cobre (Cu) sérico y ceruloplasmina bajas, con Cu en orina también bajo. No tiene clínica digestiva ni antecedentes de cirugía gastrointestinal. Las pruebas de función hepática, la ferrocinética, las cifras de Hb y leucocitos y los niveles de zinc (Zn) no presentan alteraciones relevantes. Discusión: el Cu es un oligoelemento que participa como componente de las cuproenzimas en múltiples funciones fisiológicas. Los niveles séricos bajos pueden relacionarse con causas genéticas o adquiridas, como la baja ingesta, la cirugía bariátrica, el aumento de las pérdidas, etc. Las principales manifestaciones clínicas son hematológicas (anemia, leucopenia) o neurológicas (mielopatía, neuropatía periférica). El tratamiento tiene base empírica. En los casos severos puede iniciarse con administración intravenosa, seguido de mantenimiento por vía oral.

Does Seipin Play a Role in Oxidative Stress Protection and Peroxisome Biogenesis? New Insights from Human Brain Autopsies.

Seipin is a widely expressed protein but with highest levels found in the brain and testes. Seipin function is not yet completely understood, therefore the aim of this study was to evaluate the expression of BSCL2 transcripts in the central nervous system (CNS) of humans and investigate the effect of their overexpression on a neuron model and their relationship with oxidative stress protection, as well as shed light on the pathogenic mechanisms of Celia's Encephalopathy. We analyzed the expression of BSCL2 transcripts using real-time RT-PCR in samples across the brain regions of subjects who underwent necropsy and from a case with Celia's Encephalopathy. The transcript encoding the long seipin isoform (BSCL2-203, 462 aa) is expressed primarily in the brain and its expression is inversely correlated with age in the temporal lobe, amygdala, and hypothalamus. Strong positive correlations were found between BSCL2 expression and some genes encoding protective enzymes against oxidative stress including SOD1 and SOD2, as well as peroxisome proliferator-activated receptor gamma (PPARG) in the amygdala. These results were experimentally corroborated by overexpressing BSCL2 transcripts in SH-SY5Y cells with lentiviral transduction and assessing their effects on neuron differentiated cells. Confocal microscopy studies showed that both seipin and PEX16 are closely expressed in the hypothalami of healthy human brains, and PEX16 was absent in the same region of the PELD case. We hypothesize that seipin has specific CNS functions and may play a role in peroxisome biogenesis.

Lipodystrophic laminopathies: Diagnostic clues.

The nuclear lamina is a complex reticular structure that covers the inner face of the nucleus membrane in metazoan cells. It is mainly formed by intermediate filaments called lamins, and exerts essential functions to maintain the cellular viability. Lamin A/C provides mechanical steadiness to the nucleus and regulates genetic machinery. Laminopathies are tissue-specific or systemic disorders caused by variants in LMNA gene (primary laminopathies) or in other genes encoding proteins which are playing some role in prelamin A maturation or in lamin A/C function (secondary laminopathies). Those disorders in which adipose tissue is affected are called laminopathic lipodystrophies and include type 2 familial partial lipodystrophy and certain premature aging syndromes. This work summarizes the main clinical features of these syndromes, their associated comorbidities and the clues for the differential diagnosis with other lipodystrophic disorders.

Criteria for diagnosis and postoperative control of acromegaly, and screening and management of its comorbidities: Expert consensus. / Criterios para el diagnóstico y el control poscirugía de la acromegalia, y el cribado y el manejo de sus comorbilidades: recomendaciones de expertos.

Acromegaly is a rare disease with many comorbidities that impair quality of life and limit survival. There are discrepancies in various clinical guidelines regarding diagnosis and postoperative control criteria, as well as screening and optimal management of comorbidities. This expert consensus was aimed at establishing specific recommendations for the Spanish healthcare system. The existing recommendations, the scientific evidence on which they are based, and the main controversies are reviewed. Unfortunately, the low prevalence and high clinical variability of acromegaly do not provide strong scientific evidences. To mitigate this disadvantage, a modified Delphi questionnaire, combining the best available scientific evidence with the collective judgment of experts, was used. The questionnaire, generated after a face-to-face debate, was completed by 17 Spanish endocrinologists expert in acromegaly. A high degree of consensus was reached (79.3%), as 65 of the total 82 statements raised were accepted. Some criteria for diagnosis and postoperative control were identified by this procedure. Regarding comorbidities, recommendations have been established or suggested for screening and management of oncological, cardiovascular, respiratory (sleep apnea), metabolic (dyslipidemia and diabetes), musculoskeletal, and hypopituitarism-related disorders. Consensus recommendations may facilitate and homogenize clinical care to patients with acromegaly in the Spanish health system.

Inflammatory myopathy in the context of an unusual overlapping laminopathy.

Laminopathies are genetic disorders associated with alterations in nuclear envelope proteins, known as lamins. The LMNA gene encodes lamins A and C, and LMNA mutations have been linked to diseases involving fat (type 2 familial partial lipodystrophy [FPLD2]), muscle (type 2 Emery-Dreifuss muscular dystrophy [EDMD2], type 1B limb-girdle muscular dystrophy [LGMD1B], and dilated cardiomyopathy), nerves (type 2B1 Charcot-Marie-Tooth disease), and premature aging syndromes. Moreover, overlapping syndromes have been reported. This study aimed to determine the genetic basis of an overlapping syndrome in a patient with heart disease, myopathy, and features of lipodystrophy, combined with severe metabolic syndrome. We evaluated a 54-year-old woman with rheumatoid arthritis, chronic hypercortisolism (endogenous and exogenous), and a history of cured adrenal Cushing syndrome. The patient presented with a complex disorder, including metabolic syndrome associated with mild partial lipodystrophy (Köbberling-like); mild hypertrophic cardiomyopathy, with Wolff-Parkinson- White syndrome and atrial fibrillation; and limb-girdle inflammatory myopathy. Mutational analysis of the LMNA gene showed a heterozygous c.1634G>A (p.R545H) variant in exon 10 of LMNA. This variant has previously been independently associated with FPLD2, EDMD2, LGMD1B, and heart disease. We describe a new, LMNA-associated, complex overlapping syndrome in which fat, muscle, and cardiac disturbances are related to a p.R545H variant.

Association of metreleptin treatment and dietary intervention with neurological outcomes in Celia's encephalopathy.

Celia's encephalopathy (progressive encephalopathy with/without lipodystrophy, PELD) is a recessive neurodegenerative disease that is fatal in childhood. It is caused by a c.985C>T variant in the BSCL2/seipin gene that results in an aberrant seipin protein. We evaluated neurological development before and during treatment with human recombinant leptin (metreleptin) plus a dietary intervention rich in polyunsaturated fatty acids (PUFA) in the only living patient. A 7 years and 10 months old girl affected by PELD was treated at age 3 years with metreleptin, adding at age 6 omega-3 fatty acid supplementation. Her mental age was evaluated using the Battelle Developmental Inventory Screening Test (BDI), and brain PET/MRI was performed before treatment and at age 5, 6.5, and 7.5 years. At age 7.5 years, the girl remains alive and leads a normal life for her mental age of 30 months, which increased by 4 months over the last 18 months according to BDI. PET images showed improved glucose uptake in the thalami, cerebellum, and brainstem. This patient showed a clear slowdown in neurological regression during leptin replacement plus a high PUFA diet. The aberrant BSCL2 transcript was overexpressed in SH-SY5Y cells and was treated with docosahexaenoic acid (200 µM) plus leptin (0.001 mg/ml) for 24 h. The relative expression of aberrant BSCL2 transcript was measured by qPCR. In vitro studies showed significant reduction (32%) in aberrant transcript expression. This therapeutic approach should be further studied in this devastating disease.

Inmunonutrición, evidencias y experiencias / Immunonutrition, evidence and experiences

La inmunonutrición es una ciencia que engloba aspectos relacionados con la nutrición, la inmunidad, la infección, la inflamación y el daño tisular. Las fórmulas inmunomoduladoras han demostrado beneficios en una amplia variedad de situaciones clínicas. El objetivo de este trabajo es revisar la evidencia disponible en inmunonutrición (IN). Para ello, se ha realizado una búsqueda bibliográfica con las palabras clave: inmunonutrición, arginina, glutamina, nucleótidos, ácidos grasos omega-3, ERAS, fast-track. Se han incluido ensayos clínicos, revisiones y guías de práctica clínica. La IN ha demostrado reducir las fístulas en el postoperatorio en pacientes con cáncer de cabeza y cuello. En pacientes con cáncer gástrico y cáncer de esófago, la IN se asocia a una disminución de las complicaciones infecciosas y la estancia hospitalaria. Otras situaciones clínicas que se benefician del uso de la IN son la cirugía del cáncer de páncreas, la cirugía del cáncer colorrectal y los grandes quemados. Son necesarios más estudios controlados, prospectivos y aleatorizados para confirmar los potenciales beneficios de la IN en otras situaciones clínicas como la cirugía torácica no esofágica, el cáncer vesical, la cirugía ginecológica, la fractura de cadera, la patología hepática y la COVID-19, entre otros. (AU)

Immunonutrition is a science that encompasses aspects related to nutrition, immunity, infection, inflammation and tissue damage. Immunomodulatory formulas have shown benefits in a wide variety of clinical situations.The objective of this work was to review the available evidence in immunonutrition (IN). For this, a bibliographic search has been carried outwith the keywords: immunonutrition, arginine, glutamine, nucleotides, omega-3 fatty acids, ERAS, fast-track. Clinical trials, reviews and clinicalpractice guidelines have been included.IN has been shown to reduce postoperative fistulae in head and neck cancer patients and in gastric and esophageal cancer patients, infectiouscomplications and hospital stay. Other clinical situations that benefit from the use of IN are pancreatic cancer surgery, colorectal cancer surgeryand major burns. More controlled, prospective, and randomized studies are necessary to confirm the potential benefits of IN in other clinical situations such as non-esophageal thoracic surgery, bladder cancer, gynecological surgery, hip fracture, liver pathology and COVID-19, among others. (AU)

Type 1 familial partial lipodystrophy: understanding the Köbberling syndrome.

Familial partial lipodystrophy are Mendelian disorders involving abnormal body fat distribution and insulin resistance. The current classification includes the Köbberling syndrome (type 1 familial partial lipodystrophy), characterized by fat loss in the lower limbs and abnormal fat accumulation in other areas. Type 1 familial partial lipodystrophy appears to be heritable, but little is known about it, including putative contributing mutations. We aimed to characterize this syndrome better by evaluating a group of women with phenotypic features of type 1 familial partial lipodystrophy. This is a case-controlled study in which 98 women with type 1 familial partial lipodystrophy that lacked classical mutations known to cause familial partial lipodystrophy were compared with 60 women without lipodystrophy and 25 patients with type 2 familial partial lipodystrophy (Dunnigan disease). Clinical course, body composition by dual-energy X-ray absorptiometry, HbA1c, lipid profile, insulin, leptin and family history were evaluated in all of the participants. Analyses of receiver-operating characteristic curve were performed for type 1 familial partial lipodystrophy diagnosis, comparing different truncal/limbs ratios. Among patients with type 1 familial partial lipodystrophy, 68 % developed recognizable lipodystrophy before adolescence, and most displayed an autosomal-dominant pattern (86 %). Women with type 1 familial partial lipodystrophy had less lower-limb adipose tissue than women without lipodystrophy, but significantly more than patients with Dunnigan disease. Moreover, metabolic disturbances occurred more frequently in the type 1 familial partial lipodystrophy group (81 %) than in the non-lipodystrophic group (30 %, p<0.05). The severity of metabolic disturbances was inversely proportional to the percentage of fat in the lower extremities and directly proportional to the amount of visceral adipose tissue. Metabolic profiles were worse in type 1 familial partial lipodystrophy than in Dunnigan disease. According to the receiver-operating characteristic curve analysis, the best ratio was subscapular/calf skinfolds (KöB index), with a cut-off value of 3.477 (sensitivity: 89 %; specificity: 84 %). Type 1 familial partial lipodystrophy was an early-onset, autosomal-dominant lipodystrophy, characterized by fat loss in the lower limbs and abnormal fat accumulation in the abdominal visceral region, associated to insulin resistance and metabolic disorders. A KöB index >3.477 is highly suggestive of this syndrome.

Skipped BSCL2 Transcript in Celia's Encephalopathy (PELD): New Insights on Fatty Acids Involvement, Senescence and Adipogenesis.

OBJECTIVE: PELD (Progressive Encephalopathy with or without Lipodystrophy or Celia's Encephalopathy) is a fatal and rare neurodegenerative syndrome associated with the BSCL2 mutation c.985C>T, that results in an aberrant transcript without the exon 7 (Celia seipin). The aim of this study was to evaluate both the process of cellular senescence and the effect of unsaturated fatty acids on preadipocytes from a homozygous c.985C>T patient. Also, the role of aberrant seipin isoform on adipogenesis was studied in adipose-derived human mesenchymal stem cells. MATERIAL AND METHODS: Cellular senescence was evaluated using ß-galactosidase staining of preadipocytes obtained from a homozygous c.985C>T patient. Moreover, these cells were cultured during 24 hours with Intralipid, a soybean oil-based commercial lipid emulsion. The expression of the different BSCL2 transcripts was measured by qPCR. Adipose-derived human mesenchymal stem cells were differentiated to a fat lineage using StemPRO adipogenesis kit, and the expression of BSCL2 transcripts and several adipogenesis-related genes was measured by qPCR. RESULTS: the treatment of preadipocytes with unsaturated fatty acids significantly reduced the expression of the BSCL2 transcript without exon 7 by 34 to 63%. On the other hand, at least in preadipocytes, this mutation does not disturb cellular senescence rate. Finally, during adipocyte differentiation of adipose-derived human mesenchymal stem cells, the expression of adipogenic genes (PPARG, LPIN1, and LPL) increased significantly over 14 days, and noteworthy is that the BSCL2 transcript without exon 7 was differentially expressed by 332 to 723% when compared to day 0, suggesting an underlying role in adipogenesis. CONCLUSIONS: our results suggest that Celia seipin is probably playing an underestimated role in adipocyte maturation, but not in senescence, and its expression can be modified by exogenous factors as fatty acids.

Hipocupremia severa y polineuropatía amiloidótica familiar por transtiretina / Severe hypocupremia and familial amyloid polyneuropathy

Introducción: presentamos el caso de un paciente con antecedentes de polineuropatía amiloidótica familiar por transtiretina (TTR-FAP) diagnosticado de hipocupremia severa. Caso clínico: varón de 79 años afecto de TTR-FAP. Visto en consulta de nutrición por desnutrición severa. En el estudio analítico presenta cifras de cobre (Cu) sérico y ceruloplasmina bajas, con Cu en orina también bajo. No tiene clínica digestiva ni antecedentes de cirugía gastrointestinal. Las pruebas de función hepática, la ferrocinética, las cifras de Hb y leucocitos y los niveles de zinc (Zn) no presentan alteraciones relevantes. Discusión: el Cu es un oligoelemento que participa como componente de las cuproenzimas en múltiples funciones fisiológicas. Los niveles séricos bajos pueden relacionarse con causas genéticas o adquiridas, como la baja ingesta, la cirugía bariátrica, el aumento de las pérdidas, etc. Las principales manifestaciones clínicas son hematológicas (anemia, leucopenia) o neurológicas (mielopatía, neuropatía periférica). El tratamiento tiene base empírica. En los casos severos puede iniciarse con administración intravenosa, seguido de mantenimiento por vía oral

Introduction: we report a patient with transthyretin familial amyloid polyneuropathy (TTR-FAP) and severe hypocupremia. Case report: a 79-year-old male with TTR-FAP and severe malnutrition. Laboratory tests showed low serum copper (Cu) and ceruloplasmin levels, as well as low urinary Cu levels. The patient reported neither digestive symptoms nor previous gastrointestinal surgery. Liver function tests, iron metabolism, hemoglobin, leukocytes and zinc were normal. Discussion: Cu is a trace element. It is part of the cuproenzymes involved in several physiological functions. Hypocupremia can be related to genetic or acquired etiologies, including low intake, bariatric surgery, increased losses, etc. Primary clinical manifestations include hematological (anemia and leukopenia) and neurological (myelopathy, peripheral neuropathy) features. Treatment is empirical. In severe cases it may be initiated with endovenose administration, followed by oral supplementation

Recombinant human leptin treatment in genetic lipodystrophic syndromes: the long-term Spanish experience.

Lipodystrophies are a group of diseases mainly characterized by a loss of adipose tissue and frequently associated with insulin resistance, hypertriglyceridemia, and hepatic steatosis. In uncommon lipodystrophies, these complications frequently are difficult to control with conventional therapeutic approaches. This retrospective study addressed the effectiveness of recombinant methionyl leptin (metreleptin) for improving glucose metabolism, lipid profile, and hepatic steatosis in patients with genetic lipodystrophic syndromes. We studied nine patients (five females and four males) with genetic lipodystrophies [seven with Berardinelli-Seip syndrome, one with atypical progeroid syndrome, and one with type 2 familial partial lipodystrophy (FPLD)]. Six patients were children under age 9 years, and all patients had baseline triglycerides levels >2.26 mmol/L and hepatic steatosis; six had poorly controlled diabetes mellitus. Metreleptin was self-administered subcutaneously daily at a final dose that ranged between 0.05 and 0.24 mg/(kg day) [median: 0.08 mg/(kg day)] according to the body weight. The duration of treatment ranged from 9 months to 5 years, 9 months (median: 3 years). Plasma glucose, hemoglobin A1c (Hb A1c), lipid profile, plasma insulin and leptin, and hepatic enzymes were evaluated at baseline and at least every 6 months. Except for the patient with FPLD, metreleptin replacement significantly improved metabolic control (Hb A1c: from 10.4 to 7.1 %, p < 0.05). Plasma triglycerides were reduced 76 % on average, and hepatic enzymes decreased more than 65 %. This study extends knowledge about metreleptin replacement in genetic lipodystrophies, bearing out its effectiveness for long periods of time.

Criterios para el diagnóstico y el control poscirugía de la acromegalia, y el cribado y el manejo de sus comorbilidades: recomendaciones de expertos / Criteria for diagnosis and postoperative control of acromegaly, and screening and management of its comorbidities: Expert consensus

La acromegalia es una enfermedad rara, con abundantes comorbilidades que deterioran la calidad de vida y limitan la supervivencia. Existen discrepancias en diversas guías clínicas respecto al diagnóstico y los criterios de control poscirugía, así como para el cribado y el manejo óptimo de las comorbilidades. El objetivo de este consenso de expertos ha sido establecer recomendaciones específicas para nuestro ámbito asistencial español. Hemos revisado las recomendaciones existentes, la evidencia científica que las sustentan y las principales controversias. Desafortunadamente, la baja prevalencia y la elevada variabilidad clínica de la acromegalia no permiten disponer de evidencias científicas sólidas. Para atenuar este inconveniente hemos utilizado un cuestionario Delphi modificado, que combina la mejor evidencia científica disponible con el juicio colectivo de expertos. Tras un debate presencial se generó el cuestionario que fue respondido por un grupo de 17 endocrinólogos españoles expertos en acromegalia. Se consiguió un alto grado de consenso (79,3%), aceptando 65 de un total de 82 aseveraciones planteadas. De esta manera, se han perfilado algunos criterios diagnósticos y de control poscirugía. Respecto a las comorbilidades, se han establecido o precisado recomendaciones para el cribado y el manejo de las enfermedades oncológica, cardiovascular, respiratoria (apnea del sueño), metabólica (dislipidemia y diabetes), osteoarticular e hipopituitarismo. Las recomendaciones consensuadas pueden facilitar y homogeneizar la asistencia clínica a los pacientes con acromegalia de nuestro sistema sanitario español

Acromegaly is a rare disease with many comorbidities that impair quality of life and limit survival. There are discrepancies in various clinical guidelines regarding diagnosis and postoperative control criteria, as well as screening and optimal management of comorbidities. This expert consensus was aimed at establishing specific recommendations for the Spanish healthcare system. The existing recommendations, the scientific evidence on which they are based, and the main controversies are reviewed. Unfortunately, the low prevalence and high clinical variability of acromegaly do not provide strong scientific evidences. To mitigate this disadvantage, a modified Delphi questionnaire, combining the best available scientific evidence with the collective judgment of experts, was used. The questionnaire, generated after a face-to-face debate, was completed by 17 Spanish endocrinologists expert in acromegaly. A high degree of consensus was reached (79.3%), as 65 of the total 82 statements raised were accepted. Some criteria for diagnosis and postoperative control were identified by this procedure. Regarding comorbidities, recommendations have been established or suggested for screening and management of oncological, cardiovascular, respiratory (sleep apnea), metabolic (dyslipidemia and diabetes), musculoskeletal, and hypopituitarism-related disorders. Consensus recommendations may facilitate and homogenize clinical care to patients with acromegaly in the Spanish health system

Inflammatory myopathy in the context of an unusual overlapping laminopathy

Summary Laminopathies are genetic disorders associated with alterations in nuclear envelope proteins, known as lamins. The LMNA gene encodes lamins A and C, and LMNA mutations have been linked to diseases involving fat (type 2 familial partial lipodystrophy [FPLD2]), muscle (type 2 Emery-Dreifuss muscular dystrophy [EDMD2], type 1B limb-girdle muscular dystrophy [LGMD1B], and dilated cardiomyopathy), nerves (type 2B1 Charcot-Marie-Tooth disease), and premature aging syndromes. Moreover, overlapping syndromes have been reported. This study aimed to determine the genetic basis of an overlapping syndrome in a patient with heart disease, myopathy, and features of lipodystrophy, combined with severe metabolic syndrome. We evaluated a 54-year-old woman with rheumatoid arthritis, chronic hypercortisolism (endogenous and exogenous), and a history of cured adrenal Cushing syndrome. The patient presented with a complex disorder, including metabolic syndrome associated with mild partial lipodystrophy (Köbberling-like); mild hypertrophic cardiomyopathy, with Wolff-Parkinson- White syndrome and atrial fibrillation; and limb-girdle inflammatory myopathy. Mutational analysis of the LMNA gene showed a heterozygous c.1634G>A (p.R545H) variant in exon 10 of LMNA. This variant has previously been independently associated with FPLD2, EDMD2, LGMD1B, and heart disease. We describe a new, LMNA-associated, complex overlapping syndrome in which fat, muscle, and cardiac disturbances are related to a p.R545H variant.

Acantosis nigricans en los síndromes de resistencia grave a la insulina / Acantosis nigricans in severe insulin resistance syndromes

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Síndromes lipodistróficos infrecuentes / Uncommon lipodystrophic syndromes

No disponible