Antonio Picó

Acromegaly Quality of Life Questionnaire (ACROQOL) a new health-related quality of life questionnaire for patients with acromegaly: development and psychometric properties.

objective  To develop a disease‐specific questionnaire suitable to measure health‐related quality of life (HRQOL) in acromegaly (ACROQOL).

Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults

objective To investigate the GH response to glucagon in adult patients with GH deficiency and in controls compared with the GH response to the insulin tolerance test (ITT) in patients with GH deficiency and to determine whether the use of glucagon results in a diagnostic utility test.

Serum IGF-I measured by four different immunoassays in patients with adult GH deficiency or acromegaly and in a control population

Background  IGF‐I is a useful tool in GH disorders diagnosis, however, the use of commercially available kits needs to be validated.

Prevalence of Macroprolactin Detected by Elecsys® 2010

Background: Macroprolactin or big-big PRL is, usually, a complex of little prolactin (PRL) with anti-PRL autoantibody. There are some patients with hyperprolactinemia showing a high proportion of serum macroprolactin. However, its clinical significance is not clear. Immunoassays used to determine PRL differ in their ability to detect macroprolactin. Moreover, in recent years, PRL assays have changed from isotopic methods (radioimmunoassays and immunoradiometric assays) to non-isotopic automated immunoassays. The effect of macroprolactin on currently used methods is often unknown. The aim of this work was to study the different reactivity of macroprolactin in two immunoassays systems, Elecsys 2010 and ACS Centaur, and to assess the clinical repercussion of this condition. Methods: We studied retrospectively 956 consecutive routine patients. Samples with a PRL value >636 mIU/l (211 samples) were subjected to the polyethylene glycol (PEG) precipitation test to detect macroprolactin, and 2 of them also to gel filtration chromatography for further confirmation. PRL was measured by Elecsys 2010 and, alternatively, by ACS Centaur. Results: By Elecsys 2010, macroprolactin was detected in 19 patients (9%). After removing macroprolactin, PRL levels were within the normal range in every case but one. When original sera from patients with macroprolactin were processed with ACS Centaur. PRL levels were normal or only marginally elevated. The correlation of PRL values in samples with and without macroprolactin assayed by both systems was 0.64 and 0.98, respectively. Conclusions: Nearly 9% of hyperprolactinemic patients detected by Elecsys 2010 may have macroprolactin, but the detection rate obtained using ACS Centaur is much lower. As macroprolactin seems to have minimal clinical relevance, it would be important that the users of PRL assays be aware to what extent macroprolactin interferes with their assays, and have available a validated method, such as the PEG precipitation test, to confirm the presence of macroprolactin.

Oncocytic Transformation in Pituitary Adenomas: Immunohistochemical Analyses of 65 Cases

CONTEXT Oncocytic change in pituitary adenomas has been evaluated by electron microscopy and more recently by immunohistochemistry. The clinical significance of this change is not well known, although some reports suggest a relationship with more aggressive behavior. OBJECTIVE To assess the frequency of oncocytic change in pituitary adenomas and to correlate this finding with clinicopathologic factors. DESIGN We studied oncocytic change in a series of 65 pituitary adenomas by immunohistochemistry. According to the percentage of oncocytic cells stained by antimitochondrial antibody, adenomas were classified in 3 groups: 50% or more, 10% to 49%, and 1% to 9% of oncocytic cells. RESULTS Eight cases (12.3%) showing at least 50% of oncocytic cells were classified as oncocytic adenomas: 6 were gonadotroph adenomas and 2 were null-cell adenomas. Among the remaining cases, 9 (14%; all gonadotroph adenomas) showed 10% to 49% oncocytic cells, and in 14 cases (21.5%; 5 gonadotroph adenomas, 6 somatotroph adenomas, 2 corticotroph adenomas, and 1 thyrotroph adenoma) between 1% and 9% were shown. Patients with adenomas that showed oncocytic change presented more frequently at a higher average age (P =.05), but no relationship with extrasellar extension or proliferative activity measured by Ki-67 was observed. In somatotroph adenomas, cases with oncocytic change showed higher percentages of Ki-67 (P =.05) but no correlation with extrasellar extension or cytokeratin staining (dot pattern versus perinuclear) was found. CONCLUSION Adenomas with oncocytic change present more frequently in older patients, but they are not clinically more aggressive. In addition, somatotroph adenomas with oncocytic cells show similar cytokeratin pattern and higher proliferative activity, which is not correlated with local aggressiveness.

Influence of Anti-Insulin Antibodies on Insulin Immunoassays in the Autoimmune Insulin Syndrome

The autoimmune insulin syndrome (AIS) is a rare, benign syndrome characterized by hyperinsulinaemia and hypoglycaemia associated with the presence of autoantibodies to insulin in patients who have not been treated with insulin. We report here the case of a 52-year-old patient with recurrent attacks of severe postprandial hypoglycaemia and we also present the effect of anti-insulin antibodies on insulin immunoassays. The patient was submitted to the following diagnostic tests: 5-h oral glucose tolerance test (OGTT), a prolonged 72-h fast and an insulin tolerance test (ITT). Serum glucose, total and free insulin, C-peptide, proinsulin, insulin antibodies and other autoantibodies were measured. Insulin concentrations were measured by two methods: a double antibody radioimmunoassay (RIA) and an immunoradiometric assay (IRMA). Insulin concentration measured by RIA was extremely high in the OGTT and 72-h fast. In contrast, insulin concentrations measured by IRMA were between 120 and 888 pmol/L in the OGTT and between 37 and 133 pmol/L during the 72-h fast. Fasting free-insulin concentrations measured by RIA were between 2224 and 2669 pmol/L, whereas free-insulin concentrations measured by IRMA ranged between 93 and 237 pmol/L. Total insulin concentrations measured by RIA and IRMA were 57615 and 94021 pmol/L, respectively. The C-peptide concentrations were moderately high in the three tests. Serum insulin antibody concentrations were extremely high (62–71%), compared with less than 3% in normal serum samples. In conclusion, the high insulin concentrations measured by RIA were caused by insulin autoantibodies. However, insulin concentrations measured by IRMA were not influenced by them. We conclude that IRMA is the more accurate method for measuring insulin concentrations in such cases.

Deficiencia de la hormona de crecimiento en el adulto: efectos del tratamiento sustitutivo sobre la composición corporal y la calidad de vida relacionada con la salud

Fundamento y objetivo La deficiencia de hormona de crecimiento (GH) en el adulto se acompanade alteraciones en la composicion corporal y de una disminucion de la calidad de vida relacionadacon la salud (CVRS) que pueden ser revertidas mediante la administracion de GH. Elobjetivo de este estudio fue valorar la respuesta bioquimica y sobre la composicion corporal, asicomo la CVRS y la seguridad del tratamiento sustitutivo con GH. Pacientes y metodo Se estudio a 165 pacientes con hipopituitarismo y deficiencia de GH. El disenofue de doble ciego, aleatorio, placebo-control durante un periodo de 6 meses, seguido de otros 6 enel que todos los pacientes recibieron GH. La dosis inicial fue de 0,125 UI/kg/semana, seguida de0,25 UI/kg/semana. La composicion corporal se determino mediante impedanciometria bioelectrica,y la CVRS se evaluo con los cuestionarios Perfil de Salud de Nottingham (PSN) y QoL-AGHDA. Resultados Las concentraciones de IGF-1 se incrementaron a los 6 meses en el grupo GH/GHpero no en el placebo/GH, y fueron normales para un grupo control de su mismo sexo y edad.Se observo un incremento significativo de la masa libre de grasa durante el tratamiento con GHy simultaneamente una disminucion de la masa grasa. El agua corporal total presento un aumentodurante el tratamiento. A los 6 meses se produjeron cambios en las dimensiones deenergia y reaccion emocional en ambos grupos, valoradas con el PSN, sin apreciarse modificacionesen el resto de las dimensiones. Con el QoL-AGHDA se aprecio una mejoria progresiva enla CVRS en el grupo tratado y no en el grupo placebo. Los efectos adversos se debieron fundamentalmentea retencion hidrica y se resolvieron al disminuir las dosis. Conclusiones El tratamiento con GH en adultos con deficit de esta hormona fue generalmentebien tolerado y produjo efectos beneficiosos sobre la composicion corporal y la CVRS.

Escape and lipodystrophy in acromegaly during pegvisomant therapy, a retrospective multicentre Spanish study

Pegvisomant is an effective treatment for acromegaly.

Vitamin D insufficiency and subclinical atherosclerosis in non-diabetic males living with HIV

Vitamin D insufficiency (VDI) has been associated with increased cardiovascular risk in the non‐HIV population. This study evaluates the relationship among serum 25‐hydroxyvitamin D [25(OH)D] levels, cardiovascular risk factors, adipokines, antiviral therapy (ART) and subclinical atherosclerosis in HIV‐infected males.

Guía clínica del diagnóstico y tratamiento de la apoplejía hipofisaria

La apoplejia hipofisaria (AH) es un fenomeno isquemico o hemorragico que aparece generalmente en un adenoma hipofisario. La AH se produce como consecuencia de un infarto con aparicion posterior de hemorragia y edema del tumor. La forma aguda se considera una urgencia neuroendocrinologica, ocurre de forma brusca y se caracteriza por un cuadro de cefalea brusca, junto con nauseas, vomitos, alteraciones del campo visual y afeccion de pares craneales. La forma subclinica es mas frecuente y es silente. El diagnostico de la AH se basa en un cuadro clinico tipico en el contexto de un tumor hipofisario. La AH puede provocar cualquier deficiencia hormonal hipofisaria transitoria o permanente. El deficit brusco de corticotropina y de cortisol es el mas importante, por el riesgo vital que conlleva. En el momento de la sospecha diagnostica se debe llevar a cabo una evaluacion endocrinologica con determinacion de las hormonas basales hipofisarias y las correspondientes perifericas. Posteriormente, se realizara una valoracion endocrinologica en la fase de estabilizacion encaminada a evaluar el funcionamiento remanente de la hipersecrecion hormonal, en el caso de tumores funcionantes previos, y al diagnostico de un posible hipopituitarismo permanente como secuela de la AH. Para la confirmacion de la sospecha diagnostica clinica se debe realizar una prueba de neuroimagen, una tomografia computarizada o una resonancia magnetica hipofisarias. No existe un consenso sobre el tratamiento optimo de la AH. Clasicamente, dado que el determinante de la lesion por AH es el aumento de la presion intraparaselar, la cirugia descompresiva se consideraba el tratamiento de eleccion. Sin embargo, en los ultimos anos se ha utilizado el tratamiento medico conservador con esteroides, especialmente si no existen deficit visuales.