Publications by authors named "Almudena Vicente"

7 Publications

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Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid).

Clin Neuropathol 2021 Jan-Feb;40(1):26-35

Craniopharyngiomas (CPs) are histologically benign tumors that are associated with high levels of morbidity. Two clinicopathological variants - adamantinomatous (ACP) and papillary (PCP) - have been described. They differ in their molecular features, whereby activating mutations in (V600E) and genes characterize PCP and ACP, respectively. Recently, both variants have been shown to express elevated PD-L1 protein expression, but ACP also exhibited tumor cell-intrinsic PD-1 expression. In this study we analyze these molecular alterations in 52 cases with a long follow-up and examine their associations with immunohistochemical and clinical characteristics. ACPs comprise 73.1% of cases, while 21.2% are PCPs. Aberrant nuclear immunoreactivity for β-catenin was observed in all ACPs. p.V600E mutations were observed in 90.9% of PCPs. Only one ACP case featured both alterations. Both types of CP exhibited strong nuclear staining for p63 with diffuse and basal distribution. ACP and PCP consistently expressed PD-L1, most in a substantial percentage of tumor cells, with a distinctive spatial distribution of expression in each subtype; only ACP demonstrated PD-1 expression. There was no evidence of differences in clinical prognosis between ACPs and PCPs. The identification of hallmark molecular signatures in the two CP variants is useful for sub-categorization in routine histopathology reporting. It is also pertinent to personalized therapy and for the development of improved non-invasive therapeutic strategies in this disease.
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December 2020


Neuroendocrinology 2020 Oct 9. Epub 2020 Oct 9.

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: A retrospective, multicenter, national study of CP patients diagnosed over the age of 65 years and surgically treated was performed.

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 yr)] diagnosed after the age of 65 years. The most common clinical symptoms were visual field defects (71.2%) followed by headache (45.3%). 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 (ACP) and papillary CP (PCP) 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. 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.
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October 2020

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

Endocr Connect 2019 Oct;8(10):1416-1424

Department of Endocrinology and Nutrition, Hospital Universitario Central de Asturias, Oviedo, Spain.

Primary hyperparathyroidism is the most frequent manifestation of multiple endocrine neoplasia type 1 (MEN1) syndrome. Bone and renal complications are common. Surgery is the treatment of choice, but the best timing for surgery is controversial and predictors of persistence and recurrence are not well known. Our study describes the clinical characteristics and the surgical outcomes, after surgery and in the long term, of the patients with MEN1 and primary hyperparathyroidism included in the Spanish Registry of Multiple Endocrine Neoplasia, Pheochromocytomas and Paragangliomas (REGMEN). Eighty-nine patients (49 men and 40 women, 34.2 ± 13 years old) were included. Sixty-four out of the 89 underwent surgery: a total parathyroidectomy was done in 13 patients, a subtotal parathyroidectomy in 34 and a less than subtotal parathyroidectomy in 15. Remission rates were higher after a total or a subtotal parathyroidectomy than after a less than subtotal (3/4 and 20/22 vs 7/12, P < 0.05), without significant differences in permanent hypoparathyroidism (1/5, 9/23 and 0/11, N.S.). After a median follow-up of 111 months, 20 of the 41 operated patients with long-term follow-up had persistent or recurrent hyperparathyroidism. We did not find differences in disease-free survival rates between different techniques, patients with or without permanent hypoparathyroidism and patients with different mutated exons, but a second surgery was more frequent after a less than subtotal parathyroidectomy.
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October 2019

Assessment of the outcomes of the treatment of Cushing's disease in the hospitals of Castilla-La Mancha.

Endocrinol Nutr 2015 May 2;62(5):217-23. Epub 2015 Apr 2.

Servicio de Endocrinología y Nutrición, Complejo Hospitalario Universitario de Albacete, Albacete, España.

Objective: Treatment of Cushing's disease poses interesting dilemmas in clinical practice. The aim of our study was to analyze the outcomes of the different treatments, the control and recurrence rates, and the complications derived from them.

Material And Methods: Data were collected from the clinical records of 22 patients over 18 years of age (86.4% women). They had been diagnosed with Cushing's disease between 2000 and 2012, and were monitored at Complejo Hospitalario Universitario-Albacete, Hospital Virgen de la Salud-Toledo Hospital General Universitario de Ciudad Real, Hospital Virgen de la Luz-Cuenca, Hospital Nuestra Señora del Prado-Talavera de la Reina, and Complejo Hospitalario la Mancha Centro-Alcázar de San Juan.

Results: Surgery was the treatment of choice in all patients. Biochemical cure was achieved in 72.2% of patients. Nine patients developed in the early postoperative period diabetes insipidus, which became in 2 patients only. Surprisingly, 3 patients with normal postoperative neurohypophyseal function later developed permanent diabetes insipidus. New hormone deficiencies occurred in 7 patients. Seventeen patients received ketoconazole before surgery (5 of them after surgery also), and 70% of them achieved normal urinary free cortisol levels. Three patients also received radiotherapy, and all of them were cured after a median follow-up of 85.5 months; they developed no tumors or other complications.

Conclusions: Our study reports the outcomes of management of Cushing's disease in non-reference centers for this disease, possibly giving a realistic picture of standard clinical practice for the condition in Spain.
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May 2015

[Clinical practice guideline for the diagnosis and treatment of pituitary apoplexy].

Endocrinol Nutr 2013 Dec 14;60(10):582.e1-582.e12. Epub 2013 Sep 14.

Servicio de Endocrinología y Nutrición, Hospital Virgen de la Salud, Complejo Hospitalario de Toledo, Toledo, España. Electronic address:

Unlabelled: Classic pituitary apoplexy (PA) is an acute, life-threatening clinical syndrome caused by acute hemorrhage and/or infarction of the pituitary gland. PA is considered a neuroendocrinological emergency. However, there is no consensus about the best options for PA diagnosis and management.

Objective: To develop a clinical practice guideline with a number of recommendations for diagnosis and treatment of patients with PA based on the medical evidence available, in order to help clinicians involved in their care.

Methods: The clinical guideline for diagnosis and treatment of pituitary apoplexy issued in 2006 by the Neuroendocrinology Working Group of the Spanish Society of Endocrinology and Nutrition (SEEN) and the British Clinical Practice Guideline published in 2011 were taken as the basis. The text has been adapted to the format used in most international medical journals. For this, after updated medical literature, the quality of evidence and the strength of the recommendations were evaluated using the system proposed by the Agency for Health Care Policy and Research (AHCPR).

Conclusions: Diagnosis of pituitary apoplexy should be considered in all patients with acute severe headache with or without neuro-ophthalmic signs. Patients with PA must undergo a complete history and physical examination. All patients with suspected pituitary apoplexy should have urgent blood samples drawn to test electrolytes, renal function, liver function, coagulation screen, complete blood count, and basal levels of pituitary and peripheral hormones, and to rule out adrenocorticotropic hormone (ACTH) deficiency. Formal visual field assessment should be performed when the patient is clinically stable. Magnetic resonance imaging (MRI) is the imaging test of choice to confirm diagnosis. Indications for empirical urgent corticosteroid therapy in patients with PA include hemodynamic instability, impaired consciousness, reduced visual acuity, and severe visual field defects. In patients with these severe neuro-ophthalmic signs, surgery should be considered. Surgery should preferably be performed within seven days of the onset of symptoms. Patients with mild and stable signs may be managed conservatively with careful monitoring. Treatment and long-term follow-up of patients with PA should be conducted by a multidisciplinary team consisting, amongst others, of an experienced pituitary neurosurgeon, an ophthalmologist, and an endocrinologist.
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December 2013

Patterns of iodine intake and urinary iodine concentrations during pregnancy and blood thyroid-stimulating hormone concentrations in the newborn progeny.

Thyroid 2010 Nov 18;20(11):1295-9. Epub 2010 Oct 18.

Endocrinology and Nutrition Service, Complejo Hospitalario de Toledo, Toledo, Spain.

Background: Appropriate maternal intake of iodine during pregnancy is essential for maternal thyroxine production and thyroid status of the fetus. It should be possible to enhance iodine intake during pregnancy by using iodine fortified salt or taking iodine supplements. In the present report we determined the status of iodine nutrition in pregnant women who were stratified on the basis of their history of taking or not taking iodized salt or iodine supplements. The study was performed in Toledo (Spain), a region in which prior studies have noted borderline iodine sufficiency. Iodine nutrition was assessed by measuring urinary iodine concentration (UIC) and neonatal thyrotropin (TSH).

Methods: UIC was measured in 525 pregnant women. They were grouped according to their history of iodine intake. Diet Group 1 patients (n = 69) did not take iodized salt or iodine supplements during pregnancy. Diet Group 2 patients (n = 75) took iodized salt but not iodine supplements during pregnancy. Diet Group 3 patients (n = 381) took iodine supplements during pregnancy. Plasma determinations included TSH, free thyroxine, thyroid peroxidase antibody, and thyroglobulin antibody. UIC was measured in a single urine sample from all the pregnant women. Neonatal TSH was measured in capillary spot blood from all the neonates as part of a screening for congenital metabolic abnormalities.

Results: The median UIC in all subjects was 164 μg/L (interquartile range [IR]: 116-245). The median UICs in Diet Groups 1, 2, and 3 were 134.5 (IR: 90-196), 146 (IR: 103-205), and 183 (IR: 124-261) μg/L, respectively (p = not significant [NS] for Diet Group 1 vs. 2; p < 0.01 for Diet Group 2 vs. 3; all other comparisons NS). The median (IR) TSH of the neonates in all Diet Groups was 1.0 (IR: 0.7-1.6) μU/mL. Only 2 neonates had blood TSH concentrations >5 mU/L. Neonatal blood TSH concentrations were similar in all Diet Groups.

Conclusions: In a region with a history of borderline iodine deficiency the UICs were below 150 μg/L in a substantial percentage of pregnant women who did not take iodine supplements, regardless of whether or not they took iodized salt. Our results support the use of iodine supplements from the start of the pregnancy, or even before pregnancy in women who live in regions with a history of even small degrees of iodine deficiency. In addition, neonate TSH screening is not the best tool to assess whether the iodine status in populations is ideal.
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November 2010