Maternal-fetal outcomes of pregnancies in women treated at an inborn errors of metabolism unit.

INTRODUCTION: Intermediate Inborn Errors of Metabolism (IEM) are a group of inherited diseases that include phenylketonuria (PKU), tyrosinemia II (TSII), organic acidaemias and ornithine transcarbamylase deficiency (OTCD), among others. They are increasingly more common in adults due to improved management. This has allowed more affected women to consider having children with good prospects. However, pregnancy may worsen metabolic control and/or increase maternal-fetal complications. The objective is to analyse the characteristics and outcomes of pregnancies of our patients with IEM. METHODS: Retrospective descriptive study. Pregnancies of women with IEM attended to at the adult IEM referral unit of the Hospital Universitario Virgen del Rocío were included. The qualitative variables were described as n(%) and the quantitative as P50 (P25-P75). RESULTS: 24 pregnancies were recorded: 12 newborns were healthy, 1 inherited their mother's disease, 2 had maternal phenylketonuria syndrome, 1 was stillborn (gestational week 31 + 5), 5 were spontaneous abortions and 3 were voluntarily terminated. The gestations were divided into metabolically controlled and uncontrolled. CONCLUSIONS: Pregnancy planning and multidisciplinary management through to postpartum is essential to ensure maternal and fetal health. The basis of treatment in PKU and TSII is a strict protein-limited diet. Events that increase protein catabolism in organic acidaemias and DOTC should be avoided. Further investigation of pregnancy outcomes in women with IEM is needed.

Postoperative water and electrolyte disturbances after extended endoscopic endonasal transsphenoidal surgery.

Introduction: Water and electrolyte disturbances are common after pituitary surgery and can generally be classified into transient hypotonic polyuria and transient or permanent diabetes insipidus (DI). The prevalence varies in the literature between 31-51% for transient hypotonic polyuria, 5.1-25.2% for transient DI, and 1-8.8% for permanent DI. Objective: The aim of this study was to identify the prevalence of water and electrolyte disturbances with polyuria and the preoperative and postoperative predictive factors in patients undergoing surgery with an extended endoscopic endonasal approach. Material and methods: This retrospective observational descriptive study included 203 patients with a diagnosis of pituitary adenoma who underwent their first transsphenoidal surgery via the extended endoscopic endonasal approach between April 2013 and February 2020. The diagnosis of water and electrolyte disturbances was based on the criterion for polyuria (>4 ml/kg/h). Postoperative polyuria was defined as those cases diagnosed during the immediate postsurgical period that resolved prior to discharge. Transient DI included all cases with a duration of less than 6 months but still present at hospital discharge, and permanent DI included cases lasting more than 6 months. Results: The overall prevalence of water and electrolyte disorders was 30.5% (62), and the prevalence of postoperative polyuria was 23.6% (48). The median number of desmopressin doses administered to patients with postoperative polyuria was one dose (interquartile range [IQR] 1-2), and thus the median duration of treatment was 0 days. The median initiation of desmopressin was the second day after surgery (IQR 1-2). The overall prevalence of DI was 6.89%. Among the patients with transient DI, the duration was less than 3 months in three patients (1.47%), and between 3 and 6 months in two (0.98%). Nine patients had permanent DI (4.43%). (4.43%). Conclusions: The prevalence of electrolyte disturbances in our study was high, although similar to that found in the literature. Most of the cases were transient hypotonic polyuria that resolved within one day. The prevalence of transient DI in our cohort was lower than that described in the literature, while permanent DI was similar.

How the COVID-19 pandemic has affected the training of Endocrinology and Nutrition Residents. Results of a survey by the Spanish Society of Endocrinology and Nutrition.

INTRODUCTION: COVID-19 disease has become a priority for our healthcare system. The resident physicians training in endocrinology and nutrition (E&N residents) have been integrated into the COVID-19 teams. This study has been designed with the aim of analysing the educational, occupational and health impact on E&N residents. MATERIAL AND METHODS: Cross-sectional observational study via a web survey, aimed at E&N residents who are members of the SEEN, carried out in November 2020. The following data were analysed: demographic variables, number of beds in the training hospital, alteration of rotations, integration in COVID-19 teams, participation in telemedicine, scientific activity and impact on physical and emotional health. RESULTS: 87 responses were obtained (27% of all E&N residents), 67.8% women, 28.1 ±â€¯1.8 years, 60% 4th year E&N residents. 84% participated in COVID-19 teams and 93% in the telemedicine consultations of their service. Most have had their rotations interrupted. 97.7% have participated in scientific meetings or virtual congresses and a third of them have collaborated in scientific work on COVID-19 in relation to endocrinology and nutrition. Overall, 75.8% think the pandemic has affected their mood a lot or quite a lot, and 73.8% think that the pandemic has negatively impacted their training. CONCLUSIONS: The SARS-CoV-2 pandemic has compromised the training, work activity and health of E&N residents. They have been integrated both in COVID-19 teams and in the restructured activity of their departments. However, they have managed to continue their training in virtual format and have participated in scientific work.

Cardiometabolic and Nutritional Morbidities of a Large, Adult, PKU Cohort from Andalusia.

The establishment of national neonatal screening systems has resulted in improved quality of life and life expectancy in patients with phenylketonuria (PKU). This has led to the development of multidisciplinary treatment units for adult patients with PKU. We present a retrospective descriptive study of a cohort of 90 adult patients (>16 years) with PKU under active follow-up in two reference centers in Andalusia. We analyzed disease severity, treatment type, demographic variables, cardiovascular risk factors, vitamin and hormone profiles, and bone metabolism. The median (interquartile range)age was 29 (23−38) years, 47 (52.2%) were women and 43 (47.8%) were men. Eighty (88.9%) had classical PKU, five (5.6%) moderate PKU, and five (5.6%) mild PKU. Diagnosis was by neonatal screening in 62 (68.9%) of the patients. The rest had late diagnosis. Treatment with sapropterin was given to 18 (20%) patients and diet and nutrition therapy to 72 (80%). There was adequate metabolic control according to Phe levels in 43 (47.78%) patients. Body mass index was 26.61 (22.7−31.1) kg/m2. Twenty-six (29.2%) patients had obesity, 7 (7.9%) hypertension, 2 (2.2%) type 2 diabetes, 26 (28.89%) dyslipidemia, 14 (15.6%) elevated total cholesterol, 9 (15.8%) decreased high-density lipoprotein cholesterol and 16 (17.8%) hypertriglyceridemia. Seven (10.3%) patients had osteoporosis and 28 (41.17%) osteopenia. Twenty-six (30.6%) had vitamin D (25OH) deficiency and four (4.5%) vitamin B12 deficiency. Although we observed no differences with most vascular risk factors, we found a high prevalence of obesity in relation to the age of the cohort. A continued evaluation of comorbidities in these patients is therefore needed, despite adequate metabolic control.

[How the COVID-19 pandemic has affected the training of Endocrinology and Nutrition Residents. Results of a survey by the Spanish Society of Endocrinology and Nutrition]. / Cómo ha afectado la pandemia COVID-19 en la formación de los MIR de Endocrinología y Nutrición. Resultados de una encuesta de la Sociedad Española de Endocrinología y Nutrición.

INTRODUCTION: COVID-19 disease has become a priority for our healthcare system. The resident physicians training in endocrinology and nutrition (E&N residents) have been integrated into the COVID-19 teams. This study has been designed with the aim of analysing the educational, occupational and health impact on E&N residents. MATERIAL AND METHODS: Cross-sectional observational study via a web survey, aimed at E&N residents who are members of the SEEN, carried out in November 2020. The following data were analysed: demographic variables, number of beds in the training hospital, alteration of rotations, integration in COVID-19 teams, participation in telemedicine, scientific activity and impact on physical and emotional health. RESULTS: 87 responses were obtained (27% of all E&N residents), 67.8% women, 28.1 ± 1.8 years, 60% 4th year E&N residents. 84% participated in COVID-19 teams and 93% in the telemedicine consultations of their service. Most have had their rotations interrupted. 97.7% have participated in scientific meetings or virtual congresses and a third of them have collaborated in scientific work on COVID-19 in relation to endocrinology and nutrition. Overall, 75.8% think the pandemic has affected their mood a lot or quite a lot, and 73.8% think that the pandemic has negatively impacted their training. CONCLUSIONS: The SARS-CoV-2 pandemic has compromised the training, work activity and health of E&N residents. They have been integrated both in COVID-19 teams and in the restructured activity of their departments. However, they have managed to continue their training in virtual format and have participated in scientific work.

Description of characteristics and outcomes of a cohort of patients with severe and enduring eating disorders (SE-ED).

OBJECTIVE: To describe the characteristics of the patients, as well as the treatment outcomes for the people treated in an Endocrinology and Nutrition unit with a diagnosis of SE-ED (> 7 years evolution despite evidence-based conventional treatment). METHODS: A descriptive observational study was conducted. Patients with a diagnosis of SE-ED (anorexia nervosa and bulimia nervosa) treated in the Endocrinology and Nutrition service of the Virgen del Rocío University Hospital between 2014 and 2019 were included. RESULTS: 67 patients were contacted and accepted to participate in the study. 95.5% were women. 67.2% were diagnosed with AN (anorexia nervosa) and 32.8% with BN (bulimia nervosa). Their median ages (years) at the onset of symptoms, beginning of follow-up and at present were 17, 32 and 42.5 respectively. Their median time of follow-up was 9 years. 73.1% had mental comorbitidy and AN patients had more osteoporosis (48.9% vs 22.7%, p = 0.04) and hypogonadotropic hypogonadism (31.1% vs. 4.5%, p = 0.014). DISCUSSION: The SE-ED patients in our sample began treatment years after the onset of symptoms, which may have led to their chronification. This emphasizes the importance of an early diagnosis in eating disorders. They presented with a high rate of physical complications and mental comorbidity. In the current sample, it was determined that patients with AN presented with higher rates of osteoporosis and hypogonadotropic hypogonadism than patients with BN. LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies. At present, the criteria for severe and enduring eating disorders (SE-ED) are not sufficiently clearly defined. It has been calculated that approximately 20% of patients with anorexia nervosa (AN) and 10% of patients with bulimia nervosa (BN) suffer a chronification. We evaluated the characteristics of the patients, as well as the treatment outcomes for the people treated in an Endocrinology and Nutrition unit with a diagnosis of SE-ED (which was made based on an evolution greater than 7 years despite conventional treatment). The SE-ED patients in our sample began treatment years after the onset of symptoms, which may have led to their chronification. They presented with a high rate of physical complications and mental comorbidity. In the current sample, it was determined that patients with AN presented with higher rates of osteoporosis (health condition that weakens bones, making them fragile and more likely to break) and hypogonadotropic hypogonadism (illness in which testes or ovaries produce little or no sex hormones due to a problem in the pituitary gland) than patients with BN.

Our experience in prolactinomas larger than 60mm / Nuestra experiencia en prolactinomas mayores de 60mm

INTRODUCTION: Giant prolactinomas (tumor size larger than 40mm) are a rare entity of benign nature. Prolactinomas larger than 60mm are usually underrepresented in published studies and their clinical presentation, outcomes and management might be different from smaller giant prolactinomas. PATIENTS AND METHODS: We retrospective collected data from patients with prolactinomas larger than 60mm in maximum diameter and prolactin (PRL) serum levels higher than 21,200μIU/mL in our series of prolactinomas (283). Data were collected from January 2012 to December 2017. We included three patients with prolactinomas larger than 60mm. RESULTS: At diagnosis, two patients presented neurological symptoms and one nasal protrusion. All patients received medical treatment with dopamine agonists. No surgical procedure was performed. Median prolactin levels at diagnosis was 108,180 [52,594-514,984]μIU/mL. Medical treatment achieved a marked reduction (>99%) in prolactin levels in all cases. Tumor size reduction (higher than 33%) was observed in all cases. In one patient cerebrospinal fluid (CSF) leak was observed after tumor shrinkage. CONCLUSIONS: Dopamine agonists appear to be an effective and safe first-line treatment in prolactinomas larger than 60mm even in life-threatening situations. More studies with a higher number of patients are necessary to obtain enough data to make major recommendations

INTRODUCCIÓN: Los prolactinomas gigantes (de tamaño superior a 40mm) son una entidad rara de naturaleza benigna. Los prolactinomas mayores de 60mm suelen estar infrarrepresentados en los estudios publicados, y su presentación clínica, resultados y tratamiento podrían ser diferentes de los de prolactinomas gigantes más pequeños. PACIENTES Y MÉTODOS: Recogimos retrospectivamente datos de pacientes con prolactinomas de más de 60mm de diámetro máximo y con concentraciones séricas de prolactina (PRL) superiores a 21.200μIU/ml de nuestra serie de prolactinomas (283). Los datos se recogieron entre enero de 2012 y diciembre de 2017. Se incluyeron 3 pacientes con prolactinomas mayores de 60mm. RESULTADOS: En el momento del diagnóstico, 2 pacientes presentaban síntomas neurológicos, y uno protrusión nasal. Todos los pacientes recibieron tratamiento médico con agonistas dopaminérgicos. No se realizó ninguna intervención quirúrgica. La mediana de las concentraciones de PRL al diagnóstico fue de 108.180 (52.594-514.984)μIU/ml. El tratamiento médico logró una reducción notable (>99%) de los valores de prolactina en todos los casos. En todos los casos se observó una reducción del tamaño del tumor (superior al 33%). En un paciente se observó una fuga de líquido cefalorraquídeo (LCR) tras la reducción del tumor. CONCLUSIÓN: Los agonistas dopaminérgicos parecen ser un tratamiento de primera línea eficaz y seguro en los prolactinomas mayores de 60mm incluso en situaciones peligrosas para la vida. Se necesitan más estudios con un mayor número de pacientes para obtener datos suficientes para hacer recomendaciones importantes

Our experience in prolactinomas larger than 60mm.

INTRODUCTION: Giant prolactinomas (tumor size larger than 40mm) are a rare entity of benign nature. Prolactinomas larger than 60mm are usually underrepresented in published studies and their clinical presentation, outcomes and management might be different from smaller giant prolactinomas. PATIENTS AND METHODS: We retrospective collected data from patients with prolactinomas larger than 60mm in maximum diameter and prolactin (PRL) serum levels higher than 21,200µIU/mL in our series of prolactinomas (283). Data were collected from January 2012 to December 2017. We included three patients with prolactinomas larger than 60mm. RESULTS: At diagnosis, two patients presented neurological symptoms and one nasal protrusion. All patients received medical treatment with dopamine agonists. No surgical procedure was performed. Median prolactin levels at diagnosis was 108,180 [52,594-514,984]µIU/mL. Medical treatment achieved a marked reduction (>99%) in prolactin levels in all cases. Tumor size reduction (higher than 33%) was observed in all cases. In one patient cerebrospinal fluid (CSF) leak was observed after tumor shrinkage. CONCLUSIONS: Dopamine agonists appear to be an effective and safe first-line treatment in prolactinomas larger than 60mm even in life-threatening situations. More studies with a higher number of patients are necessary to obtain enough data to make major recommendations.

A Silent Corticotroph Pituitary Carcinoma: Lessons From an Exceptional Case Report.

Nowadays, neither imaging nor pathology evaluation can accurately predict the aggressiveness or treatment resistance of pituitary tumors at diagnosis. However, histological examination can provide useful information that might alert clinicians about the nature of pituitary tumors. Here, we describe our experience with a silent corticothoph tumor with unusual pathology, aggressive local invasion and metastatic dissemination during follow-up. We present a 61-year-old man with third cranial nerve palsy at presentation due to invasive pituitary tumor. Subtotal surgical approach was performed with a diagnosis of silent corticotroph tumor but with unusual histological features (nuclear atypia, frequent multinucleation and mitotic figures, and Ki-67 labeling index up to 70%). After a rapid regrowth, a second surgical intervention achieved successful debulking. Temozolomide treatment followed by stereotactic fractionated radiotherapy associated with temozolomide successfully managed the primary tumor. However, sacral metastasis showed up 6 months after radiotherapy treatment. Due to aggressive distant behavior, a carboplatine-etoposide scheme was decided but the patient died of urinary sepsis 31 months after the first symptoms. Our case report shows how the presentation of a pituitary tumor with aggressive features should raise a suspicion of malignancy and the need of follow up by multidisciplinary team with experience in its management. Metastases may occur even if the primary tumor is well controlled.

Craniopharyngioma in the Elderly: A Multicenter and Nationwide Study in Spain.

BACKGROUND: Craniopharyngioma (CP) is a rare tumor in the elderly whose clinical features and prognosis are not well known in this population. AIM: To evaluate the clinicopathological features and therapeutic outcomes of CP diagnosed in the elderly. PATIENTS AND METHODS: This was a retrospective, multicenter, national study of CP patients diagnosed over the age of 65 years and surgically treated. RESULTS: From a total of 384 adult CP patients, we selected 53 (13.8%) patients (27 women [50.9%], mean age 72.3 ± 5.1 years [range 65-83 years]) diagnosed after the age of 65 years. The most common clinical symptoms were visual field defects (71.2%) followed by headache (45.3%). The maximum tumor diameter was 2.9 ± 1.1 cm. In most patients, the tumor was suprasellar (96.2%) and mixed (solid-cystic) (58.5%). The surgical approach most commonly used was transcranial surgery (52.8%), and more than half of the patients (54.7%) underwent subtotal resection (STR). Adamantinomatous CP and papillary CP were present in 51 and 45.1%, respectively, with mixed forms in the remaining. Surgery was accompanied by an improvement in visual field defects and in headaches; however, pituitary hormonal hypofunction increased, mainly at the expense of an increase in the prevalence of diabetes insipidus (DI) (from 3.9 to 69.2%). Near-total resection (NTR) was associated with a higher prevalence of DI compared with subtotal resection (87.5 vs. 53.6%, p = 0.008). Patients were followed for 46.7 ± 40.8 months. The mortality rate was 39.6% with a median survival time of 88 (95% CI: 57-118) months. DI at last visit was associated with a lower survival. CONCLUSION: CP diagnosed in the elderly shows a similar distribution by sex and histologic forms than that diagnosed at younger ages. At presentation, visual field alterations and headaches are the main clinical symptoms which improve substantially with surgery. However, surgery, mainly NTR, is accompanied by worsening of pituitary function, especially DI, which seems to be a predictor of mortality in this population.

Combinación de acidemia metilmalónica y homocisteinuria; a propósito de un caso / Combined methylmalonic acidemia and homocystinuria; a case report

La combinación de homocistinuria con acidemia metilmalónica es un error congénito del metabolismo de la vitamina B12 o cobalamina. Es una patología poco frecuente de herencia autosómica recesiva en la que existen diversas variantes en función de la patogenia del trastorno metabólico (cblC, cblD, cblF y cblJ). La más frecuente y más grave es la variante cblC, que suele manifestarse en los primeros meses de vida, aunque se han reportado casos al inicio de la edad adulta. Se hace fundamental un correcto diagnóstico y un abordaje terapéutico eficaz. Presentamos el caso clínico de una paciente de 18 años con antecedentes personales de epilepsia que acude por fracaso renal agudo con necesidad de terapia renal sustitutiva diagnosticándose de homocistinuria con acidemia metilmalónica variante cblC (AU)

Combined methylmalonic acidemia and homocystinuria is an inborn error of metabolism of vitamin B12 or cobalamin. It´s a rare autosomal recessive disease in which there are several variants depending on the pathogenesis of the metabolic disorder (cblC, cblD, cblF and cblJ). The more frequent and more severe is the cblC variant, which usually manifests in the first months of life, although some cases have been reported at the beginning of adulthood. A proper diagnosis and effective therapeutic approach is fundamental. We report the case of a patient of 18 years with a history of epilepsy who consults for acute renal failure requiring renal replacement therapy and diagnosed with combined methylmalonic acidemia and homocystinuria cblC variant (AU)

[Combined methylmalonic acidemia and homocystinuria; a case report]. / Combinación de acidemia metilmalónica y homocisteinuria; a propósito de un caso.

Combined methylmalonic acidemia and homocystinuria is an inborn error of metabolism of vitamin B12 or cobalamin. It's a rare autosomal recessive disease in which there are several variants depending on the pathogenesis of the metabolic disorder (cblC, cblD, cblF and cblJ). The more frequent and more severe is the cblC variant, which usually manifests in the first months of life, although some cases have been reported at the beginning of adulthood. A proper diagnosis and effective therapeutic approach is fundamental. We report the case of a patient of 18 years with a history of epilepsy who consults for acute renal failure requiring renal replacement therapy and diagnosed with combined methylmalonic acidemia and homocystinuria cblC variant.

La combinación de homocistinuria con acidemia metilmalónica es un error congénito del metabolismo de la vitamina B12 o cobalamina. Es una patología poco frecuente de herencia autosómica recesiva en la que existen diversas variantes en función de la patogenia del trastorno metabólico (cblC, cblD, cblF y cblJ). La más frecuente y más grave es la variante cblC, que suele manifestarse en los primeros meses de vida, aunque se han reportado casos al inicio de la edad adulta. Se hace fundamental un correcto diagnóstico y un abordaje terapéutico eficaz. Presentamos el caso clínico de una paciente de 18 años con antecedentes personales de epilepsia que acude por fracaso renal agudo con necesidad de terapia renal sustitutiva diagnosticándose de homocistinuria con acidemia metilmalónica variante cblC.

Afección hepática en adolescente con diabetes mellitus tipo 1 y mal control metabólico / Hepatic involvement in a teenager with type1 diabetes and poor metabolic control

Las alteraciones hepáticas en la diabetes pueden ser muy diversas; la más frecuente es la enfermedad de hígado graso no alcohólico. La glucogenosis hepática adquirida es un cuadro caracterizado por acumulación de glucógeno intrahepatocitaria en la diabetes mellitus tipo 1 mal controlada y en tratamiento con altas dosis de insulina. Se presenta el caso de un adolescente diabético con una elevación progresiva de fermentos hepáticos junto con mal control metabólico. Tras descartar otras causas de hepatopatía, se llegó al diagnóstico clínico de glucogenosis hepática secundaria por la recuperación de los parámetros tras la mejoría del control glucémico sin necesidad de realizar biopsia hepática. La glucogenosis hepática secundaria es un proceso quizá más frecuente de lo publicado, reversible y con buena evolución en función del control metabólico. El diagnóstico puede ser clínico y la biopsia hepática debería reservarse a los pacientes sin mejoría tras alcanzar un mejor control glucémico (AU)

There are several manifestations of hepatic involvement in diabetes but the most frequent is non-alcoholic steatohepatitis. Acquired hepatic glycogenosis is characterized by intrahepatocyte glycogen accumulation in poorly controlled type 1 diabetes under treatment with high doses of insulin. We report the case of a diabetic teenager with progressive elevation of liver enzymes associated with poor metabolic control. After ruling out other causes of hepatic derangement, we made a clinical diagnosis of secondary hepatic glycogenosis without performing liver biopsy, as all parameters improved after better glycemic control was achieved. Secondary hepatic glycogenosis is probably more frequent than previously reported. This process is reversible and has a benign clinical course that depends on good metabolic control. Diagnosis can be made clinically. Liver biopsy should be reserved for patients with no improvement in liver tests after good metabolic control has been achieved (AU)

Hepatic involvement in a teenager with type 1 diabetes and poor metabolic control.

There are several manifestations of hepaticinvolvement in diabetes but the most frequent is non-alcoholic steatohepatitis. Acquired hepatic glycogenosis is characterized by intrahepatocyte glycogen accumulation in poorly controlled type 1 diabetes under treatment with high doses of insulin. We report the case of a diabetic teenager with progressive elevation of liver enzymes associated with poor metabolic control. After ruling out other causes of hepatic derangement, we made a clinical diagnosis of secondary hepatic glycogenosis without performing liver biopsy, as all parameters improved after better glycemic control was achieved. Secondary hepatic glycogenosis is probably more frequent than previously reported. This process is reversible and has a benign clinical course that depends on good metabolic control. Diagnosis can be made clinically. Liver biopsy should be reserved for patients with no improvement in liver tests after good metabolic control has been achieved.