RESUMEN
PURPOSE: Mitotane is the only approved treatment for metastatic adrenocortical carcinoma (ACC). Monitoring plasma levels is recommended, but its predictive value is insufficient. METHODS: This prospective study of the French ENDOCAN-COMETE network aimed to investigate the prognostic role of plasma mitotane levels pharmacokinetics and free or bound to lipoprotein fraction measurements during six consecutive months. Lipoprotein fractions were isolated by ultracentrifugation, and mitotane level was determined by HPLC-UV. Total, free, and lipoprotein fraction bound plasma mitotane were monitored every two months for six months with morphological assessment. The primary endpoint was overall survival (OS). RESULTS: 21 patients with metastatic ACC were included. Median overall survival was 23 months. The median free mitotane level per patient was 12% (± 7%), and the majority (88%) was bound to lipoprotein fractions. Several pharmacokinetics measures of total mitotane were related to OS: first level at one month (p = 0.026), mean level (p = 0.055), and area under the curve (AUC) (p = 0.048), with higher exposure associated to longer OS. Free mitotane (not bounded) and mitotane bounded to lipoprotein subfraction added no prognostic values. The relationship between the mitotane level and OS suggested a minimum "effective" threshold of 10-15 mg/L or an area under the curve above 100 mg/L/month with no individualized maximum value. CONCLUSION: This prospective study did not identify any added prognostic value of free mitotane level over the total level. Early total mitotane level measurements (before 3-6 months) were related to OS with a higher and faster exposure related to more prolonged survival.
RESUMEN
OBJECTIVE: Adrenocortical carcinoma (ACC) has an aggressive but variable clinical course. Prognostic stratification based on the European Network for the Study of Adrenal Tumours stage and Ki67 index is limited. We aimed to demonstrate the prognostic role of a points-based score (S-GRAS) in a large cohort of patients with ACC. DESIGN: This is a multicentre, retrospective study on ACC patients who underwent adrenalectomy. METHODS: The S-GRAS score was calculated as a sum of the following points: tumour stage (1-2 = 0; 3 = 1; 4 = 2), grade (Ki67 index 0-9% = 0; 10-19% = 1; ≥20% = 2 points), resection status (R0 = 0; RX = 1; R1 = 2; R2 = 3), age (<50 years = 0; ≥50 years = 1), symptoms (no = 0; yes = 1), and categorised, generating four groups (0-1, 2-3, 4-5, and 6-9). Endpoints were progression-free survival (PFS) and disease-specific survival (DSS). The discriminative performance of S-GRAS and its components was tested by Harrell's Concordance index (C-index) and Royston-Sauerbrei's R2D statistic. RESULTS: We included 942 ACC patients. The S-GRAS score showed superior prognostic performance for both PFS and DSS, with best discrimination obtained using the individual scores (0-9) (C-index = 0.73, R2D = 0.30, and C-index = 0.79, R2D = 0.45, respectively, all P < 0.01vs each component). The superiority of S-GRAS score remained when comparing patients treated or not with adjuvant mitotane (n = 481 vs 314). In particular, the risk of recurrence was significantly reduced as a result of adjuvant mitotane only in patients with S-GRAS 4-5. CONCLUSION: The prognostic performance of S-GRAS is superior to tumour stage and Ki67 in operated ACC patients, independently from adjuvant mitotane. S-GRAS score provides a new important guide for personalised management of ACC (i.e. radiological surveillance and adjuvant treatment).
Asunto(s)
Neoplasias de la Corteza Suprarrenal/diagnóstico , Carcinoma Corticosuprarrenal/diagnóstico , Técnicas de Diagnóstico Endocrino , Neoplasias de la Corteza Suprarrenal/mortalidad , Neoplasias de la Corteza Suprarrenal/patología , Neoplasias de la Corteza Suprarrenal/cirugía , Adrenalectomía , Carcinoma Corticosuprarrenal/mortalidad , Carcinoma Corticosuprarrenal/patología , Carcinoma Corticosuprarrenal/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Proyectos de Investigación , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: The clinical course of advanced adrenocortical carcinoma (ACC) is heterogeneous. Our study aimed primarily to refine and make headway in the prognostic stratification of advanced ACC. PATIENTS AND METHODS: Patients with advanced ENSAT ACC (stage III or stage IV) at diagnosis registered between 2000 and 2009 in the ENSAT database were enrolled. The primary end point was overall survival (OS). Parameters of potential prognostic relevance were selected. Univariate and multivariate analyses were carried out: model 1 'before surgery'; model 2 'post-surgery'. RESULTS: Four hundred and forty-four patients with advanced ENSAT ACC (stage III: 210; stage IV: 234) were analyzed. After a median follow-up of 55.2 months, the median OS was 24 months. A modified ENSAT (mENSAT) classification was validated: stage III (invasion of surrounding tissues/organs or the vena renalis/cava) and stage IVa, IVb, IVc (2, 3 or >3 metastatic organs, including N, respectively). Two- or 5-year OS was 73%, 46%, 26% and 15% or 50%, 15%, 14% and 2% for stages III, IVa, IVb and IVc, respectively. In the multivariate analysis, mENSAT stages (stages IVa, IVb, or IVc, respectively) were significantly correlated with OS (P < 0.0001), as well as additional parameters: age ≥ 50 years (P < 0.0001), tumor- or hormone-related symptoms (P = 0.01 and 0.03, respectively) in model 1 but also the R status (P = 0.001) and Grade (Weiss >6 and/or Ki67 ≥ 20%, P = 0.06) in model 2. CONCLUSION: The mENSAT classification and GRAS parameters (Grade, R status, Age and Symptoms) were found to best stratify the prognosis of patients with advanced ACC.
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Neoplasias de la Corteza Suprarrenal/patología , Carcinoma Corticosuprarrenal/patología , Neoplasias Óseas/secundario , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Recurrencia Local de Neoplasia/patología , Neoplasias de la Corteza Suprarrenal/mortalidad , Carcinoma Corticosuprarrenal/mortalidad , Neoplasias Óseas/mortalidad , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Pulmonares/mortalidad , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by fetal macrosomia, macroglossia, and abdominal wall defects. BWS patients are at risk to develop Wilms tumor, neuroblastoma, hepatoblastoma, and adrenal tumors. A young woman with BWS features, but with inconclusive genetic evidence for the disease, came to clinical observation for signs of virilization at the age of 16 years. An adrenocortical tumor was diagnosed and surgically resected. The tumor underwent 2 local relapses that were also surgically treated. The patient was also operated to remove a breast fibroadenoma. SNP arrays were used to analyze chromosome abnormalities in normal and tumor samples from the patient and her parents. The patient presented genome-wide mosaic paternal uniparental disomy (patUPD) both in the adrenocortical and the breast tumors, with different degrees of loss of heterozygosity (LOH). The more recent relapses of the adrenocortical tumor showed a loss of part of chromosome 17p that was absent in the first tumor. Analysis of a skin biopsy sample also showed mosaic patUPD with partial LOH, while no LOH was detected in leukocyte DNA. This case shows that virilizing adrenocortical tumors may be a clinical feature of patients with BWS. The SNP array technology is useful to diagnose genome-wide patUPD mosaicism in BWS patients with an inconclusive molecular diagnosis and underlines the tumorigenic potential of the absence of the maternal genome combined with an excess of the paternal genome.
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Neoplasias de la Corteza Suprarrenal/genética , Síndrome de Beckwith-Wiedemann/genética , Disomía Uniparental , Virilismo/genética , Adolescente , Femenino , Hirsutismo/genética , Humanos , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
BACKGROUND: Point mutations of the PRKAR1A gene are a genetic cause of Carney complex (CNC) and primary pigmented nodular adrenocortical disease (PPNAD), but in 30% of the patients no mutation is detected. OBJECTIVE: Set up a routine-based technique for systematic detection of large deletions or duplications of this gene and functionally characterize these mutations. METHODS: Multiplex ligation-dependent probe amplification (MLPA) of the 12 exons of the PRKAR1A gene was validated and used to detect large rearrangements in 13 typical CNC and 39 confirmed or putative PPNAD without any mutations of the gene. An in-frame deletion was characterized by western blot and bioluminescence resonant energy transfer technique for its interaction with the catalytic subunit. RESULTS: MLPA allowed identification of exons 3-6 deletion in three patients of a family with typical CNC. The truncated protein is expressed, but rapidly degraded, and does not interact with the protein kinase A catalytic subunit. CONCLUSIONS: MLPA is a powerful technique that may be used following the lack of mutations detected by direct sequencing in patients with bona fide CNC or PPNAD. We report here one such new deletion, as an example. However, these gene defects are not a frequent cause of CNC or PPNAD.
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Complejo de Carney/genética , Subunidad RIalfa de la Proteína Quinasa Dependiente de AMP Cíclico/genética , Eliminación de Gen , Reordenamiento Génico , Adolescente , Enfermedades de la Corteza Suprarrenal/genética , Enfermedades de la Corteza Suprarrenal/metabolismo , Adulto , Complejo de Carney/metabolismo , Dominio Catalítico , Subunidad RIalfa de la Proteína Quinasa Dependiente de AMP Cíclico/química , Subunidad RIalfa de la Proteína Quinasa Dependiente de AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/química , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Exones , Salud de la Familia , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Estabilidad Proteica , Adulto JovenRESUMEN
Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Local and distant recurrences occur in a subset of tumors classified as 'aggressive' ACC (aACC), as opposed to 'non-aggressive' ACC (naACC). In this study, we investigated whether tissue and serum microRNAs (miRNAs) are predictive of ACC prognosis. Tissue miRNA expression profiles were determined using microarrays in a test series of six adrenocortical adenomas (ACAs), six naACCs, and six aACCs. Eight miRNAs were selected for further validation by quantitative RT-PCR (ten ACAs, nine naACCs, nine aACCs, and three normal adrenals). Serum levels of five miRNAs were measured in samples from 56 subjects (19 healthy controls (HC), 14 ACA, nine naACC, and 14 aACC patients). MiR-195 and miR-335 levels were significantly decreased in both tumor and serum samples of ACC patients relative to ACA patients or HC. MiR-139-5p and miR-376a levels were significantly increased in aACC compared with naACC patients in tumor samples only. Tissue miR-483-5p was markedly upregulated in a majority of ACC compared with ACA patients or HC, but most importantly, serum miR-483-5p was detected only in aACC patients. High circulating levels of miR-483-5p or low circulating levels of miR-195 were associated with both shorter recurrence-free survival (P=0.0004 and P=0.0014 respectively) and shorter overall survival (P=0.0005 and P=0.0086 respectively). In conclusion, this study reports for the first time that circulating miR-483-5p and miR-195 are promising noninvasive biomarkers with a highly specific prognostic value for the clinical outcome of ACC patients.
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Neoplasias de la Corteza Suprarrenal/metabolismo , Carcinoma Corticosuprarrenal/metabolismo , MicroARNs/metabolismo , Adolescente , Neoplasias de la Corteza Suprarrenal/genética , Carcinoma Corticosuprarrenal/genética , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Adulto JovenRESUMEN
OBJECTIVE: We designed a single-center retrospective study to assess the QT interval duration and to describe cardio vascular events among patients treated with mitotane for a adrenocortical carcinoma (ACC). DESIGN: We selected 14 patients (6 males and 8 females) that met the following criteria: ACC treated with mitotane, for whom an electrocardiogram (ECG) at baseline (before mitotane initiation) was available and for whom at least one ECG was available during the course of mitotane therapy together with a concomitant mitotane plasma level determination. RESULTS: Mean mitotane plasma level at baseline and after treatment showed a significant increase (mean level increased from 0 to 14.9±2 mg/l). At baseline and before mitotane was initiated all QTc intervals were <450 msec for men and <460 msec for women. During the treatment phase with mitotane, no QTc>470 msec was found in any patients respectively for men and women. In addition, no patient showed any significant QTc prolongation (>5% or >10 msec) at any time during mitotane treatment. During a mean follow-up of 15.9±3.5 months (range 2-45 months). No cardiovascular deaths or hospitalization for cardiovascular events was documented. No torsades de pointes were documented on ECG. No syncope, dizziness, heart failure were observed during follow up. Six out of 14 patients died during the follow-up, in five cases due to the progression of the disease, one patient died suddenly at home during followup. CONCLUSION: This short and retrospective series shows no evidence that mitotane induce any QT prolongation, even when plasma levels are well above the therapeutic window.
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Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Antineoplásicos Hormonales/uso terapéutico , Síndrome de QT Prolongado/prevención & control , Mitotano/uso terapéutico , Neoplasias de la Corteza Suprarrenal/complicaciones , Carcinoma Corticosuprarrenal/complicaciones , Adulto , Anciano , Electrocardiografía , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Síndrome de QT Prolongado/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Endocrine pancreatic tumors (EPTs) are uncommon tumors, representing 1-2% of all pancreatic neoplasms. They are categorized on the basis of their clinical features into functioning and non-functioning tumors. EPTs may be part of the multiple endocrine neoplasia type 1 (MEN 1), an autosomal dominant syndrome due to inactivating germline mutation of the menin gene. Somatic mutations of menin are present in about 20% of sporadic neoplasms, particularly gastrinomas and insulinomas. 30-75% of patients with MEN1 have EPTs. The most prevalent are the gastrinomas (20-60%), then the insulinomas (5-10%), the glucagonamas and VIPomas (6-10%), whereas the nonfunctioning EPTs are present in 20-40% of patients. The most important biochemical screening marker for EPTs is chromogranin A, as it increases in 50-80% of patients. The most important negative prognostic factors are the presence of metastases, the gross invasion of adjacent organs, the angioinvasion, the perineural invasion and an immunopositivity for Ki-67 > 2%. Among the different imaging techniques, echoendoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) are indicated for the detection of the primary tumor, but (III)In-octreotide scintigraphy has the highest sensitivity for detecting metastases. The choice of treatment is still debated and is different when the tumor occurs as a part of the MEN syndrome. The surgical treatment is the first choice for insulinomas and is more controversial for gastrinomas. The medical treatment includes somatostatin analogues (SA), chemotherapy and interferon-alpha (IFN-alpha). SA seem to improve the symptoms and have an antiproliferative effect, the most striking effect being seen in patients with VIPomas. Chemotherapy, which is generally proposed as a combination of streptozotocin (STZ) and 5-fluorouracil (5-FU) or doxorubicin, is indicated when the tumors tend to grow. Interferon-alpha (IFN-alpha) stimulates the immune system, blocks the tumor cells in the G1/S-phase of the cell cycle, inhibits protein and hormone synthesis and inhibits angionenesis. Treatment with IFN has been shown to produce symptomatic response in 40-60% of patients, a biochemical response in 30-60% and tumor shrinkage in 10-15%.
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Carcinoma de Células de los Islotes Pancreáticos , Neoplasia Endocrina Múltiple Tipo 1 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células de los Islotes Pancreáticos/diagnóstico , Carcinoma de Células de los Islotes Pancreáticos/epidemiología , Carcinoma de Células de los Islotes Pancreáticos/patología , Carcinoma de Células de los Islotes Pancreáticos/terapia , Humanos , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/epidemiología , Neoplasia Endocrina Múltiple Tipo 1/patología , Neoplasia Endocrina Múltiple Tipo 1/terapia , PronósticoRESUMEN
The primary adrenal localization of a non-Hodgkin's lymphoma (NHL) is a rare event. We report the case of a 70-yr-old woman, who was admitted at our Institute for a hormonal evaluation after the incidental discovery of a right adrenal mass during ultrasonography (US) performed for cardiovascular disease. At the physical examination, no sign of adrenal hyperfunction was present. She showed only an androgenetic alopecia and her blood pressure was 180/70 mm Hg, with an arrhythmic heart rate of 100 beats/min. No alterations in hormonal and biochemical data were observed. US studies showed a right adrenal mass (major diameter 16 mm), and an abdominal computed tomography (CT) scan confirmed this solid lesion (major diameter 15 mm) with a high density. [75Se] methylnorcholesterol adrenal scintigraphy exhibited a normal symmetrical radiotracer uptake. After 8 months of follow-up, an abdominal CT scan demonstrated a significant increase of the right adrenal mass (major diameter: 40 mm), with a solid tissue density and enhancement after i.v. contrast. [75Se] methylnorcholesterol adrenal scintigraphy showed an absent uptake on the right side versus the contralateral side. The hematological, hormonal and radiological evaluation did not reveal any sign of malignancy. Owing to the mass enlargement and the modification of scintigraphic pattern, the patient underwent unilateral adrenalectomy. Histological examination revealed a primary diffuse large B-cell NHL (REAL classification) of the adrenal gland. After surgery, she underwent a combined polychemotherapy (cyclophospamide, adriamycin, vincristine and prednisone) and subsequently one cycle of radiotherapy. At present, the patient is in good conditions and there are no signs or symptoms of recurrent disease.
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Neoplasias de las Glándulas Suprarrenales/diagnóstico , Linfoma de Células B/diagnóstico , Linfoma no Hodgkin/terapia , Neoplasias de las Glándulas Suprarrenales/cirugía , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Femenino , Humanos , Hallazgos Incidentales , Linfoma de Células B/terapiaRESUMEN
Since the optimal glucocorticoid replacement needs to avoid over and under treatment, the adequacy of different daily cortisone acetate (CA) doses was assessed in 34 patients with primary and central hypoadrenalism. The conventional twice CA 37.5 mg/day dose was administered to all patients (A regimen: 25 mg at 07:00 h, 12.5 mg at 15:00 h), while in 2 subgroups of 12 patients the dose was shifted on 2 thrice daily regimens (B: 25 mg at 07:00, 6.25 mg at 12: 00, 6.25 mg at 17:00; C: 12.5 mg, 12.5 mg, 12.5 mg). In other 12 patients the conventional dose was reduced to a thrice 25 mg/day administration (D regimen: 12.5 mg, 6.25 mg, 6.25 mg). In all patients, urinary free cortisol (UFC) excretion and cortisol day curves were evaluated. During the CA 37.5 mg administration, nadir cortisol levels were significantly higher with the thrice daily regimens (143 +/- 31 on B and 151 +/- 34 nmol/l on C) than with the conventional twice (85 +/- 16 nmol/l). Moreover, UFC, morning cortisol levels and mean cortisol day curves were similar in each group. Finally, during D regimen nadir cortisol levels were higher than in A and similar to B and C regimens. No difference in UFC and in cortisol day curves by reducing the CA dose was found. In conclusion, the thrice daily cortisone regimens, in which more physiological cortisol levels are achieved, perform better as replacement therapy. The administration of 25 mg/day CA confirms that replacement therapy is more adequate with a lower dose, particularly in patients with central hypoadrenalism.
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Insuficiencia Suprarrenal/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Terapia de Reemplazo de Hormonas , Adulto , Anciano , Cortisona/administración & dosificación , Cortisona/análogos & derivados , Cortisona/uso terapéutico , Esquema de Medicación , Femenino , Humanos , Hidrocortisona/sangre , Hidrocortisona/orina , Masculino , Persona de Mediana EdadRESUMEN
Little is known about the pathogenesis of adrenocortical tumors. The cAMP-dependent pathway is physiologically activated by ACTH in adrenocortical cells and different components of this cascade may be altered in some functioning adrenocortical tumors. Recently, mutations of the gene encoding the PKA type 1 A regulatory subunit (R1 A), PRKAR1A, associated with loss of heterozygosity (LOH) at PRKAR1A locus, have been demonstrated in primary pigmented nodular adrenocortical disease (PPNAD), either isolated or associated with Carney complex. Moreover, activating mutations of the Gs(alpha) gene (the gsp oncogene) have also been found in a small number of adrenocortical cortisol-secreting adenomas. Aim of this study was to investigate the presence of such genetic alterations on a series of 10 ACTH-independent Cushing syndrome due to non-PPNAD adrenocortical adenomas. The coding sequence of PRKAR1A, evaluated by PCR and direct sequencing analysis, revealed the absence of mutations while heterozygosity for at least 1 polymorphism excluded LOH in most tumors. In one single adenoma gsp mutation was detected. In conclusion, we provide additional evidence that the only mutational changes able to activate the cAMP pathway so far identified, i.e. PRKAR1A mutations and gsp oncogene, are a rare event in adrenocortical tumors.
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Neoplasias de la Corteza Suprarrenal/genética , Análisis Mutacional de ADN , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Proteínas/genética , Neoplasias de la Corteza Suprarrenal/enzimología , Adulto , Anciano , AMP Cíclico/fisiología , Subunidad RIalfa de la Proteína Quinasa Dependiente de AMP Cíclico , Proteínas Quinasas Dependientes de AMP Cíclico , Femenino , Humanos , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
Oral DHEA administration to patients with hypoadrenalism, in addition to glucocorticoid and mineralcorticoid replacement, may improve both well-being and hormonal/metabolic parameters. Twenty patients (13 men, 7 women, 26-76 yr, 11 with Addison's disease, 9 with central hypoadrenalism) were recruited in a placebo-controlled, randomized study. Hormone levels, carbohydrate and lipid parameters, bone metabolism, body composition and psychological parameters were evaluated at baseline and after treatment with DHEA 50 mg/day or placebo for 4 months. After 4 months of DHEA administration, serum DHEAS levels raised both in men (from 0.71+/-0.18 to 8.28+/-1.66 micropmol/l, p<0.005) and in women (from 0.25+/-0.07 to 5.65+/-1.93 micromol/l, p<0.05). Only in hypoadrenal women an increase in testosterone (T; from 0.4+/-0.1 to 1.45+/-0.26 nmol/l, p<0.05) and androstenedione (A; from 0.86+/-0.34 to 2.05+/-0.29 nmol/l, p<0.05) levels was observed. In men no significant modifications in T and 17-hydroxyprogesterone (17-OHP) levels were found, whereas serum SHBG significantly decreased. As far as the metabolic parameters are concerned, only in patients with Addison's disease a significant decrease in total cholesterol and in low-density lipoproteins after 4 months of DHEA administration was found. No changes in glucose metabolism and insulin sensitivity were observed. In basal conditions, mean serum osteocalcin (OC) was normal and significantly decreased after DHEA treatment. A significant reduction in body fat mass percentage (BF%) after DHEA administration was observed. As far as well-being is concerned, DHEA replacement did not cause any relevant variation of subjective health scales and sexuality in both sexes. Our study confirms that DHEA may be beneficial for female patients with hypoadrenalism, mainly in restoring androgen levels. Concerning the health status, more sensitive and specific instruments to measure the effects of DHEA treatment could be necessary.
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Insuficiencia Suprarrenal/tratamiento farmacológico , Conducta/fisiología , Deshidroepiandrosterona/uso terapéutico , Hormonas/sangre , Enfermedad de Addison/tratamiento farmacológico , Enfermedad de Addison/metabolismo , Enfermedad de Addison/psicología , Insuficiencia Suprarrenal/metabolismo , Insuficiencia Suprarrenal/psicología , Adulto , Afecto/efectos de los fármacos , Anciano , Androstenodiona/sangre , Glucemia/metabolismo , Composición Corporal/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/metabolismo , Deshidroepiandrosterona/administración & dosificación , Deshidroepiandrosterona/efectos adversos , Sulfato de Deshidroepiandrosterona/sangre , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Caracteres Sexuales , Testosterona/sangreAsunto(s)
Síndrome de Cushing/sangre , Antígeno Prostático Específico/sangre , Hormona Adrenocorticotrópica/sangre , Adulto , Androstenodiona/sangre , Síndrome de Cushing/cirugía , Sulfato de Deshidroepiandrosterona/sangre , Femenino , Hormonas Esteroides Gonadales/sangre , Hirsutismo/sangre , Humanos , Hidrocortisona/sangre , Testosterona/sangreRESUMEN
BACKGROUND: The surgical success rate in macroprolactinomas is quite low, while medical treatment is more effective in reducing PRL levels and tumour mass. In this study the effectiveness of surgical, medical and radiant approaches on clinical symptoms, PRL levels and tumour size were compared in a large series of patients with macroprolactinomas. METHODS: One hundred and thirty-two patients (63 males and 69 females) were followed-up. Eighty-three patients were operated by trans-sphenoidal (TSS) approach: 18 underwent only TSS, 10 were operated and then irradiated; 30 patients underwent TSS and dopamine agonists, 25 were treated by TSS, radiotherapy and dopamine agonists. One hundred and four patients were treated by medical therapy: 49 patients were only administered dopamine agonists and 55 were given dopamine agonists after unsuccessful surgery and/or radiotherapy. RESULTS: In 83 patients serum PRL levels decreased from 1873+/-319.9 ng/ml to 831.6+/-297.8 ng/ml after trans-sphenoidal surgery: a significant PRL reduction was obtained in 18 cases (22%) and a full PRL normalization was found in 15 patients (18%). The pituitary adenoma was completely removed in the 15 cases, in whom serum PRL normalized. Sexual function was restored in 57 percent; of women and in 29 percent; of men. In contrast, dopaminergic drugs normalized PRL levels (from 1590.5+/-232.7 to 19.2+/-4.8 ng/ml) in 93/104 patients (89 percent;). Sexual function was restored in 74 percent; of women and in 75 percent; of men. Radiotherapy, performed after unsuccessful TSS, was ineffective in normalizing PRL levels. CONCLUSIONS: Medical therapy should be considered the first choice treatment in macroprolactinomas, while the surgical approach is recommended when neurological compressive symptoms are present and in patients resistant or intolerant to dopamine agonists. Radiotherapy may be indicated only in the patients in whom medical and surgical therapy have not been successful.