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Anorexia nervosa (AN) is a severe psychiatric disorder characterized by a harmful persistence of self-imposed starvation resulting in significant weight loss. Research suggests that alterations in the nucleus accumbens (NAcc) and circulating endocannabinoids (eCBs), such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may contribute to increased severity and maladaptive behaviors in AN, warranting an examination of the interplay between central reward circuitry and eCBs. For this purpose, we assessed NAcc functional connectivity and circulating AEA and 2-AG concentrations in 18 individuals with AN and 18 healthy controls (HC) to test associations between circulating eCBs, NAcc functional connectivity, and AN severity, as defined by body mass index (BMI). Decreased connectivity was observed between the NAcc and the right insula (NAcc-insula; pFWE < 0.001) and the left supplementary motor area (NAcc-SMA; pFWE < 0.001) in the AN group compared to HC. Reduced NAcc-insula functional connectivity mediated the association between AEA concentrations and BMI in the AN group. However, in HC, NAcc-SMA functional connectivity had a mediating role between AEA concentrations and BMI. Although no significant differences in eCBs concentrations were observed between the groups, our findings provide insights into how the interaction between eCBs and NAcc functional connectivity influences AN severity. Altered NAcc-insula and NAcc-SMA connectivity in AN may impair the integration of interoceptive, somatosensory, and motor planning information related to reward stimuli. Furthermore, the distinct associations between eCBs concentrations and NAcc functional connectivity in AN and HC could have clinical implications for weight maintenance, with eCBs being a potential target for AN treatment.
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Anorexia Nerviosa , Núcleo Accumbens , Humanos , Endocannabinoides , Imagen por Resonancia Magnética , RecompensaRESUMEN
AIM: To investigate the impact of pituitary surgery on glucose metabolism and to identify predictors of remission of diabetes after pituitary surgery in patients with acromegaly. METHODS: A national multicenter retrospective study of patients with acromegaly undergoing transsphenoidal surgery for the first time at 33 tertiary Spanish hospitals (ACRO-SPAIN study) was performed. Surgical remission of acromegaly was evaluated according to the 2000 and 2010 criteria. RESULTS: A total of 604 acromegaly patients were included in the study with a total median follow up of 91 months (interquartile range [IQR] 45-163). At the acromegaly diagnosis, 23.8% of the patients had diabetes mellitus (DM) with a median glycated hemoglobin (HbA1c) of 6.9% (IQR 6.4-7.9) [51.9 mmol/mol (IQR 46.4-62.8)]. In the multivariate analysis, older age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), dyslipidemia (OR 5.25, 95% CI 2.81 to 9.79), arthropathy (OR 1.39, 95% CI 2.82 to 9.79), and higher IGF-I levels (OR 1.30, 95% CI 1.05 to 1.60) were associated with a greater prevalence of DM. At the last follow-up visit after surgery, 21.1% of the DM patients (56.7% of them with surgical remission of acromegaly) experienced diabetes remission. The cure rate of DM was more common in older patients (hazard ratio [HR] 1.77, 95% CI 1.31 to 2.43), when surgical cure was achieved (HR 2.10, 95% CI 1.01 to 4.37) and when anterior pituitary function was not affected after surgery (HR 3.38, 95% CI 1.17 to 9.75). CONCLUSION: Glucose metabolism improved in patients with acromegaly after surgery and 21% of the diabetic patients experienced diabetes remission; being more frequent in patients of older age, and those who experienced surgical cure and those with preserved anterior pituitary function after surgery.
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Knowledge of ectopic insulinomas comes from single cases. We performed a systematic review through PubMed, Web of Science, Embase, eLibrary and ScienceDirect of all cases reported in the last four decades. We also describe one unreported patient. From 28 patients with ectopic insulinoma, 78.6% were female and mean age was 55.7 ± 19.2 years. Hypoglycaemia was the first symptom in 85.7% while 14.3% complained of abdominal pain or genital symptoms. Median tumour diameter was 27.5 [15-52.5] mm and it was localised by CT (73.1%), MRI (88.9%), [68Ga]Ga-DOTA-exedin-4 PET/CT (100%), 68Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC (100%), somatostatin receptor scintigraphy (40%) and endoscopic ultrasound (50%). Ectopic insulinomas were located at duodenum (n = 3), jejunum (n = 2), and one respectively at stomach, liver, appendix, rectum, mesentery, ligament of Treitz, gastrosplenic ligament, hepatoduodenal ligament and splenic hilum. Seven insulinomas were affecting the female reproductive organs: ovary (n = 5), cervix (n = 2) and remaining tumours were at retroperitoneum (n = 3), kidney (n = 2), spleen (n = 1) and pelvis (n = 1). 89.3% underwent surgery (66.7% surgery vs. 33.3% laparoscopy) and 16% underwent an ineffective pancreatectomy. 85.7% had localized disease at diagnosis and 14.3% developed distant metastasis. Median follow-up time was 14.5 [4.5-35.5] months and mortality was reported in 28.6% with median time until death of 60 [5-144] months. In conclusion, ectopic insulinomas are presented as hypoglycaemia with female preponderance. Functional imaging [68Ga]Ga-DOTA-exedin-4 PET/CT and 68Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC have very high sensitivity. Clinicians should be alert to the possibility of extra-pancreatic insulinomas when classic diagnostic tests and intraoperative pancreas exploration failed to locate the tumour.
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Hipoglucemia , Insulinoma , Neoplasias Pancreáticas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioisótopos de Galio , Insulinoma/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , SomatostatinaRESUMEN
BACKGROUND: In recent years, dopamine agonists (DAs) have become an attractive therapeutic option to prevent both tumor growth and post-surgical tumor remnant growth in clinically non-functioning pituitary adenoma (NFPA). AIM: To analyze our experience on the effect of cabergoline (CAB) on tumor remnant after initial surgery in NFPA patients. PATIENTS AND METHODS: A retrospective and multicenter study of NFPA patients with tumor remnant after surgery treated with CAB was performed. RESULTS: From a total of 142 NFPA patients (79 men, 55.2%; mean age 57.2 ± 14.2 year) who underwent surgery, we selected 62/142 (43.7%) patients (32 men, 51.6%; mean age 59.3 ± 13.9 year) with tumor persistence (TP) after surgery. In 22/62 (35.5%) TP patients CAB was used (CAB group), while the rest of the patients (40/62, 64.5%) underwent active surveillance [observation (OBS) group)]. The maximum diameter of the tumor remnant did not change significantly in either the CAB group [11.5 (6.0-16.9) mm vs. 12.0 (7.0-15.0) mm, p = 0.85) or the OBS group [8.5 (6.0-13.7) mm vs. 9.0 (6.2-14.0) mm, p = 0.064) at the end of the follow-up [13 (10.5-17) vs. 77.5 (50.2-107.2) months, CAB vs. OBS group; p < 0.001]. At the end of the treatment period with CAB most of the patients (n = 20/22, 90.9%) showed no progression of the tumor remnant [stable disease, SD (n = 17/22, 77.2%) and partial response, PR (n = 3/22, 13.6%)], while 2/22 patients (9.1%) exhibited progression. Similar response rates were observed in the OBS group [SD (n = 32/40, 80%), PR (n = 2/40, 5%), and progression (n = 6/40, 15%)]. Although no statistically significant differences (p = 0.42) were found in these responses, the percentage of progression was 1.65 times higher in the OBS group compared to the CAB group. On the contrary, the percentage of PR was 2.72 times higher in the CAB group compared to the OBS group, despite a significantly shorter follow-up period in the CAB group. CONCLUSION: Although the present study showed no significant differences in the type of tumor response between the CAB and OBS groups of patients, the percentage of PR was higher and that of progression lower in the CAB group compared to the OBS group. This finding does not rule out a potential therapeutic benefit of CAB in the management of tumor remnant in patients with NFPA undergoing surgery.
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Neoplasias Hipofisarias , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Cabergolina/uso terapéutico , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Estudios Retrospectivos , Resultado del Tratamiento , Agonistas de Dopamina/uso terapéuticoRESUMEN
Knowledge of ectopic Cushing's syndrome (CS) due to thymic neuroendocrine tumours (NETs) comes from short series or single cases. Our aim is to perform a systematic review using PubMed, Embase, Scopus, Ovid Medline and Biosis Previews of all cases with ectopic CS due to thymic NETs reported in the last 40 years and describe one illustrative patient attended in our institution. Search of literature: From 162 patients, 58.6% were male and mean age was 34.6 ± 13.9 years-old. Median of symptoms until diagnosis was 6 [2-24] months and 62% had aggressive CS. Imaging was positive in 93.7% (chest X-ray), 97.8% (computed tomography), 80.7% (somatostatin receptor scintigraphy) and median tumour size was 47 [25-68.5] mm. At presentation, 18% had localized disease, 26.2% locally invasive and 55.7% advanced. Eighty-eight present underwent surgery and histological subtypes were atypical (46.7%), typical (30.4%) and carcinoma (21.7%). Tumour persisted or recurred in 70.1%, 63% received radiotherapy and 45.2% chemotherapy. Follow-up median was 26.6 [14.5-57.5] months and mortality was reported in 35.8% with median survival of 38 [19-60] months. MEN-1 mutation was referred in 3.1%. Comparatively, carcinomas had aggressive CS more frequently while atypical showed advanced disease more often. In conclusion, thymic NETs causing ectopic CS are presented as aggressive hypercortisolism in the middle aged population. The disease is commonly extended at diagnosis and persists or recurs after surgery in most patients with a short term high mortality.
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Síndrome de ACTH Ectópico , Síndrome de Cushing , Tumores Neuroendocrinos , Timoma , Neoplasias del Timo , Síndrome de ACTH Ectópico/complicaciones , Síndrome de ACTH Ectópico/diagnóstico , Síndrome de ACTH Ectópico/cirugía , Adulto , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiología , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/complicaciones , Timoma/complicaciones , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/patología , Neoplasias del Timo/cirugía , Adulto JovenRESUMEN
Pheochromocytoma/paraganglioma (Pheo/PGL) associated with pituitary adenoma (PA) is rare in clinical practice, and a common pathogenic mechanism has been suggested owing to the germline pathogenic variants found in some cases. Our aim is to propose a reassignment for a recurrent MEN1 genetic variant found in a 54-year-old male patient with bilateral pheochromocytoma and GH-secreting PA. Pheo/PGL genes study was carried out in DNA samples from Pheo as well as PA and no pathological variants or large deletions were detected. Additionally, a MEN1 gene analysis was performed, and a heterozygous germline variant in exon 10: c.1618C>T; p.(Pro540Ser) was found. No MEN1 gene deletions/duplications were detected. In evaluating a causal relationship between the c.1618C>T MEN1 variant and both tumors, we took into account that missense variants are common pathogenic variants in MEN1, and the population frequency of this variant is too high to be considered pathogenic. His son (aged 38 and carrier) is asymptomatic, and computational analysis showed discrepancies. We propose that this recurrent variant, previously considered as likely pathogenic, subsequently as variant of uncertain significance, and likely benign should now be reclassified as benign.
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Paraganglioma/genética , Feocromocitoma/genética , Neoplasias Hipofisarias/genética , Proteínas Proto-Oncogénicas/genética , Adulto , Mutación de Línea Germinal , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Paraganglioma/complicaciones , Paraganglioma/patología , Feocromocitoma/complicaciones , Feocromocitoma/patología , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/patologíaRESUMEN
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.
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Envejecimiento , Craneofaringioma , Neoplasias Hipofisarias , Anciano , Anciano de 80 o más Años , Craneofaringioma/diagnóstico , Craneofaringioma/mortalidad , Craneofaringioma/patología , Craneofaringioma/terapia , Femenino , Humanos , Masculino , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/mortalidad , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/terapia , Estudios Retrospectivos , España/epidemiologíaRESUMEN
PURPOSE AND METHODS: Sarcomas of the sellar region are uncommon and unexpected tumors. Here, we review the cases reported in literature via a systematic search. RESULTS: Ninety-four patients, 58.5% male with mean age of 39.2 ± 17.2 years were included. Fifty-seven (62%) had soft tissue sarcomas (STS) and 35 (38%) bone sarcomas (BS). Sarcoma was a primary tumor in 66%, developed after radiotherapy in 31.9% and 7.4% were metastatic. Median time between radiotherapy and sarcoma development was 10.5 (11) years. Main presentation symptoms were visual disorders (87.9%), headache (61.5%) and III cranial nerve palsy (24.1%). After surgery, sarcoma persisted or recurred in 82.3% and overall mortality reported was 44.6% with 6.5 (14) months of median survival. Tumor appeared earlier in BS compared to STS (34.4 ± 15.1 vs. 42.6 ± 17.6 years), p = 0.034 and complete tumor resection was achieved more often (41.3% vs. 4.4%), p = < 0.001. Condrosarcoma and rhabdomyosarcoma were more frequent subtypes among primary tumors while fibrosarcoma was among post-radiation sarcomas. Tumor size was larger in radiation associated sarcomas (mean maximum diameter 46.3 ± 9.3 vs. 29.1 ± 8.0 mm, p = 0.004) and persistency/recurrence was similar in both groups (70.1 vs. 73.3%, p = 0.259). CONCLUSION: Sarcomas appear as mass effect symptoms in the middle aged population, mainly as primary tumors, but one third is associated with radiotherapy. Surgery is commonly not curative, mortality rate is high and death ensues shortly after diagnosis.
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Neoplasias de los Tejidos Blandos/epidemiología , Adulto , Animales , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Sarcoma/epidemiologíaRESUMEN
In 2017, the World Health Organization established that pituicytoma, granular cell tumor (GCT), spindle cell oncocytoma (SCO) and sellar ependymomas (SE) are posterior pituitary tumors (PPT). They probably arise from the pituicytes and may constitute a unique histopathological entity. We carried out a systematic review using PubMed's database. A total of 266 patients with pathological diagnosis of PPT (135 pituicytomas, 69 GCT, 47 SCO, 8 SE and 7 mixed histology tumors) were analyzed. Gender distribution was identical and median age at diagnosis was 48 ± 21.8 years. Main presentation symptoms were visual disorders (n = 142; 58.1%), headache (n = 99; 40.5%), hypopituitarism (n = 84; 34.4%), hypercortisolism (n = 10; 4.1%), polyuriapolydipsia (n = 6; 2.4%) and acromegaly features (n = 5; 2.0%). On MRI, 122 (47.6%) patients showed sellar with suprasellar extension masses, 67 (23.1%) were suprasellar and 63 (24.6%) exclusively sellar. Median tumor size was 22.0 ± 14.2 mm. Two hundred sixty four patients underwent surgery, transphenoidal access was selected in 132 (64.4%) and craniotomy in 58 (28.3%). Complications were hypopituitarism (n = 70; 42.1%), diabetes insipidus (n = 55; 33.1%) and hemorrhage (n = 50; 30.1%). Tumor persisted in 93 patients (45.6%) and recurred in 13 (6.4%). Regarding comparison between main types of PPT, SCO patients were diagnosed later (60.0 vs 47.0 vs 47.0 years, p = 0.023), the tumor was larger 25.0 mm [10.8] vs 20.0 mm [14.2] vs 2.0 mm [15.0] and they were frequently sellar with suprasellar extension tumors (71.7% vs 46.2% vs 32.8%, p = 0.003) compared to pituicytoma and GCT. In conclusion, PPT are rare tumors and have been misdiagnosed mainly as non-functioning pituitary adenomas. Different types of PPT share similar epidemiology, clinical manifestations and surgical outcomes. Surgery is the only curative option but complications and subtotal resection are common.
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Neoplasias Hipofisarias/diagnóstico , Animales , Tumor de Células Granulares/diagnóstico , Tumor de Células Granulares/diagnóstico por imagen , Humanos , Neoplasias Hipofisarias/diagnóstico por imagenRESUMEN
INTRODUCTION: Evidence suggests that food addiction (FA) is prevalent among individuals with obesity seeking bariatric surgery (BS), but there is no evidence about whether FA is a predictor of weight loss (WL). We aimed to analyse the prevalence of FA in patients with obesity seeking BS and to examine whether FA could predict WL following dietary intervention before surgery. METHOD: The study included 110 patients with obesity who underwent a dietetic intervention. Assessment included endocrinological variables, a semistructured interview to rule out mental disorders, and Yale Food Addiction Scale version 2.0 (YFAS 2.0). RESULTS: In our sample, the prevalence of FA was 26.4%. Those who met YFAS 2.0 criteria showed less WL after dietetic intervention and regain weight during dietary intervention. CONCLUSIONS: FA appears to be prevalent in obesity. Our findings confirmed a lower WL throughout dietary intervention before surgery in patients who fulfilled baseline criteria for FA. Future interventions should include multidisciplinary intervention to maximize WL before and after BS.
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Cirugía Bariátrica/psicología , Adicción a la Comida/epidemiología , Obesidad/dietoterapia , Pérdida de Peso , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/cirugía , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento , Adulto JovenRESUMEN
Carcinoid crisis (CC) has classically been considered the extreme end of the spectrum of carcinoid syndrome (CS). However, this presumption and other aspects of CC remain poorly understood. Consequently, current clinical guidelines are based on a low quality of evidence. There is no standard definition of CC and its incidence is unknown. Patients with florid CS and elevated serotonin (or its derivatives) which develop CC have been reported during decades. Nevertheless, the hypothesis that CC is due to the sudden massive release of serotonin or other vasoactive substances is unproven. Many triggers of CC (surgery, anaesthesia, peptide receptor radionuclide therapy, tumour biopsy or liver-directed treatments) have been proposed. However, data from studies are heterogeneous and even contradictory. Finally, the role of octreotide in the prevention of CC has been questioned. Herein, we report a clinical case and perform a critical review of the evidence available today on this topic.
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Síndrome Carcinoide Maligno , Humanos , Síndrome Carcinoide Maligno/terapia , Octreótido/uso terapéutico , SerotoninaRESUMEN
Rathke's cleft cysts (RCC) are a common type of lesion found in the sellar or suprasellar area. They are usually monitored clinically, but in some cases, surgery may be required. However, their natural progression is not yet well understood, and the outcomes of surgery are uncertain. The objective of this study is to evaluate the natural history of Rathke's cleft cysts in patients who are clinically monitored without treatment, and to determine the outcomes of surgery and the incidence of recurrences over time. Design and patients: National multicentric study of patients diagnosed of Rathke's cleft cyst (RCC- Spain) from 2000 onwards and followed in 15 tertiary centers of Spain. A total of 177 patients diagnosed of RCC followed for 67.3 months (6-215) and 88 patients who underwent surgery, (81 patients underwent immediate surgery after diagnosis and 7 later for subsequent growth) followed for 68.8 months (3-235). Results: The cyst size remained stable or decreased in 73.5% (133) of the patients. Only 44 patients (24.3%) experienced a cyst increase and 9 of them (5.1%) experienced an increase greater than 3 mm. In most of the patients who underwent surgery headaches and visual alterations improved, recurrence was observed in 8 (9.1%) after a median time of 96 months, and no predictors of recurrence were discovered. Conclusions: Rathke's cleft cysts without initial compressive symptoms have a low probability of growth, so conservative management is recommended. Patients who undergo transsphenoidal surgery experience rapid clinical improvement, and recurrences are infrequent. However, they can occur after a long period of time, although no predictors of recurrence have been identified.
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Quistes del Sistema Nervioso Central , Humanos , Quistes del Sistema Nervioso Central/cirugía , Quistes del Sistema Nervioso Central/patología , Femenino , Masculino , España/epidemiología , Adulto , Persona de Mediana Edad , Adulto Joven , Adolescente , Resultado del Tratamiento , Anciano , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Progresión de la Enfermedad , Estudios de Seguimiento , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , NiñoRESUMEN
OBJECTIVE: The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin cosecreting PA (GH&PRL-PA). DESIGN: This is a retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least 6 months of first-line medical treatment. METHODS: Baseline characteristics, first-line medical treatment strategies, and outcomes were analyzed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality. RESULTS: Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs 51.9 ± 12.7 years, P < .01) and harboring more frequently macroadenomas (89.7% vs 72.1%, P = .03). First-generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs 15.2%, P < .01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs 55.1%, P = .04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline. CONCLUSION: In GH&PRL-PA, the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first-line medical treatment in combination with fgSRLs in these subgroups of patients.
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Acromegalia , Cabergolina , Prolactina , Humanos , Acromegalia/tratamiento farmacológico , Acromegalia/sangre , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Cabergolina/uso terapéutico , Resultado del Tratamiento , Prolactina/sangre , Adenoma Hipofisario Secretor de Hormona del Crecimiento/tratamiento farmacológico , Adenoma Hipofisario Secretor de Hormona del Crecimiento/sangre , Adenoma Hipofisario Secretor de Hormona del Crecimiento/metabolismo , Hormona de Crecimiento Humana , Adenoma/tratamiento farmacológico , Adenoma/sangre , Adenoma/metabolismo , Adenoma/complicaciones , Anciano , Quimioterapia Combinada , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/complicaciones , España/epidemiologíaRESUMEN
PURPOSE: To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). METHODS: Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). RESULTS: GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. CONCLUSIONS: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.
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The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.
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Acromegalia , Hormona de Crecimiento Humana , Tumores Neuroendocrinos , Prolactina , Somatostatina , Humanos , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Masculino , Femenino , Hormona de Crecimiento Humana/análogos & derivados , Hormona de Crecimiento Humana/uso terapéutico , Persona de Mediana Edad , Adulto , Prolactina/sangre , Prolactina/metabolismo , Estudios Retrospectivos , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/metabolismo , Acromegalia/tratamiento farmacológico , Acromegalia/metabolismo , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/metabolismo , Anciano , Adulto JovenRESUMEN
The term hypophysitis is used to designate a heterogeneous group of pituitary conditions characterized by the presence of inflammatory infiltration of the adenohypophysis, neurohypophysis, or both. Although hypophysitis are rare disorders, the most common in clinical practice is lymphocytic hypophysitis, a primary hypophysitis characterized by lymphocytic infiltration, which predominantly affects women. Other forms of primary hypophysitis are associated with different autoimmune diseases. Hypophysitis can also be secondary to other disorders such as sellar and parasellar diseases, systemic diseases, paraneoplastic syndromes, infections, and drugs, including immune checkpoint inhibitors. The diagnostic evaluation should always include pituitary function tests and other analytical tests based on the suspected diagnosis. Pituitary magnetic resonance imaging is the investigation of choice for the morphological assessment of hypophysitis. Glucocorticoids are the mainstay of treatment for most symptomatic hypophysitis.
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Hipofisitis Autoinmune , Hipofisitis , Enfermedades de la Hipófisis , Femenino , Humanos , Neuroendocrinología , Consenso , Hipofisitis/diagnóstico , Hipofisitis/terapia , Hipofisitis/complicaciones , Hipófisis , Hipofisitis Autoinmune/diagnóstico , Hipofisitis Autoinmune/terapia , Hipofisitis Autoinmune/complicaciones , Enfermedades de la Hipófisis/diagnóstico , Enfermedades de la Hipófisis/terapiaRESUMEN
Knowledge of xanthogranuloma (XG) of the sellar region comes from short series or single cases. We performed a systematic review, using the PubMed, Web of Science, Embase, Scopus, eLibrary, and BIOSIS Preview databases, of all cases reported from 2000 to the present. We also describe one unreported patient treated in our institution. A search of the literature revealed that of 71 patients 50.7% were male and that mean age at diagnosis was 34.7 ± 19.2 years old. Median time from clinical onset until diagnosis was 7 (3-21) months. Hypopituitarism (70.4%), visual disorders (64.7%), headache (53.5%), and polyuria-polydipsia (28.2%) were the most common symptoms. On MRI, median tumor size was 20 (16-29) mm, while 71.8% were sellar/suprasellar and less frequently exclusively suprasellar (15.5%) or sellar (12.7%). On T1-weighted imaging, XG was hyperintense in 76.3% of patients, while it showed variable appearance on T2-weighted imaging. The tumor showed cystic features in 50.7%, gadolinium enhancement in 45.1%, and calcification in 22.5% of patients. All patients underwent surgery (77.4% transphenoidal approach and 18.3% craniotomy), with hypopituitarism (56.4%), diabetes insipidus (34.5%), and visual defects (7.3%) being the most common complications. Total/subtotal resection was achieved in 93.5%, while the tumor was partially removed in 6.6%. Median follow-up was 24 (6-55) months and no tumor recurrence or remnant growth was reported in 97.5% of cases. In conclusion, XG affects the younger population, manifested by hormonal deficit and mass effect symptoms. Surgery is safe and offers excellent outcomes, though hypopituitarism is frequent post-surgery. Tumor recurrence or remnant growth is rare and radiological surveillance is a good option for patients with remnant lesions.
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Diabetes Insípida , Hipopituitarismo , Humanos , Masculino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Femenino , Silla Turca/diagnóstico por imagen , Silla Turca/cirugía , Silla Turca/patología , Medios de Contraste , Gadolinio , Hipopituitarismo/complicaciones , Granuloma/patologíaRESUMEN
Current guidelines recommend temozolomide as the first-line chemotherapy for aggressive pituitary neuroendocrine tumours. However, no clinical trials have been conducted to date and clinical experience is quite limited. We retrospectively analyzed 28 patients (9 women and 19 men), aged 46.6 + 16.9, with aggressive pituitary tumours (4 pituitary carcinomas and 24 aggressive adenomas) treated with temozolomide in 10 Spanish pituitary reference centres. Four patients had Cushing's disease, 9 prolactinomas and 15 clinically non-functioning pituitary tumours (seven silent corticotroph, three silent somatotroph, one silent lactotroph, one silent gondotroph and three null-cell tumours). Median size at diagnosis was 10.5 cm3 (IQR 4.7-22.5), with cavernous sinus invasion in 88% and no metastases. Pre-temozolomide treatment, these data were 5.2 cm3 (IQR 1.9-12.3), 89.3% and 14.3% (2 intracranial and 2 spinal metastases). All patients had undergone surgery (1-5 surgeries), 25 (89.3%) had received radiotherapy (7 of them reirradiated) and 13(46.4%) had received cabergoline. One patient interrupted temozolomide prematurely. The remaining 27 patients received a median of 13 cycles (range 3-66) of 5 days every 28 days, with a mean initial dose of 265 ± 73 mg when administered alone and of 133 ± 15 mg when co-administered with radiotherapy. Eight patients (29.6%) had a significant reduction (>30%) in tumour volume and 14 (51.9%) attained tumour stabilization. After a median follow-up of 29 months (IQR 10-55), 8 out of these 22 showed disease progression. A longer progression-free survival was found in the five patients who received concomitant radiotherapy. Seven patients (25%) died (all of them because of tumour progression or complications of treatments) at 77 months (IQR 42-136) after diagnosis and 29 months (IQR 16-55) after the first dose of temozolomide. Adverse effects occurred in 18 patients (14 mild and 4 moderate or severe). In conclusion, temozolomide is an effective medical treatment for aggressive pitNET and pituitary carcinomas but is sometimes followed by tumour progression. Co-administration with radiotherapy may increase progression-free survival.
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Tumores Neuroendocrinos , Enfermedades de la Hipófisis , Neoplasias Hipofisarias , Masculino , Humanos , Femenino , Neoplasias Hipofisarias/tratamiento farmacológico , Temozolomida/uso terapéutico , España , Estudios RetrospectivosRESUMEN
BACKGROUND: Little is known about the relationship between signal intensity patterns on T2-weighted magnetic resonance imaging (MRI) in non-functioning pituitary adenomas (NFPAs). OBJECTIVE: In this study, the clinical, hormonal, histological features, and therapeutic responses were evaluated according to the T2 signal intensity in NFPAs. METHODS: This retrospective and multicenter study included a group of 166 NFPA patients (93 men, 56%, mean age 58.5 ±14.8 yr). RESULTS: Approximately half of the tumors (n=84, 50.6%) were hyperintense, while 34.3% (n=57) and 15.1% (n=25) were iso- and hypointense, respectively. The median maximum tumor diameter of the isointense group [16 (13-25) mm] was significantly lower than that of the hyperintense [23 (16.6-29.7) mm] group (p=0.003). Similarly, the tumor volume of the isointense group [1,523 (618-5,226) mm3] was significantly lower than that of the hyperintense [4,012 (2,506-8,320) mm3] group (p=0.002). Chiasmatic compression occurred less frequently in tumors with isointense signal characteristics (38.6%) compared to tumors with hypointense (68%) and hyperintense (65.5%) signal characteristics (p=0.003). Invasive adenomas (p=0.001) and the degree of cavernous sinus invasion (p<0.001) were more frequent in the hyperintense adenoma group compared to the remaining groups. Plurihormonal tumors and silent lactotroph adenomas were more frequent in the isointense tumor group. CONCLUSION: In conclusion, hyperintensity on T2-weighted MRI in NFPAs is associated with larger and more invasive tumors compared to isointense NFPAs.