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Hormônio do Crescimento Humano , Prolactina , Somatostatina , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Humanos , Prolactina/metabolismo , Prolactina/sangue , Hormônio do Crescimento Humano/análogos & derivados , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/metabolismo , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/metabolismoRESUMO
Medical treatment of acromegaly is currently performed through a trial-error approach using first generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response. Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated. METHODS AND SUBJECTS: prospective trial (21 university hospitals) comparing the effectiveness and time-to control of two treatment protocols during 12 months: A) A personalized protocol in which first option were fgSRLs as monotherapy or in combination with pegvisomant or, pegvisomant as monotherapy depending on the short Acute Octreotide Test (sAOT) results, tumor T2 Magnetic Resonance (MRI) signal or immunostaining for E-cadherin and, B) A control group with treatment always started by fgSRLs and the other drugs included after demonstrating inadequate control. RESULTS: Eighty-five patients participated; 45 in the personalized and 40 in the control group. More patients in the personalized protocol achieved hormonal control compared to those in the control group (78% vs 53%, p < 0.05). Survival analysis revealed a hazard ratio for achieving hormonal control adjusted by age and sex of 2.53 (CI 1.30-4.80). Patients from personalized arm were controlled in a shorter period of time (p = 0.01). CONCLUSION: Personalized medicine is feasible using a relatively simple protocol and allows a higher number of patients achieving control in a shorter period of time.
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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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PURPOSE: To identify clinical and radiological factors associated with a higher risk of developing a severe pituitary apoplexy (PA). METHODS: Multicenter retrospective study of patients presenting with clinical PA in three Spanish tertiary hospitals of Madrid between 2008 and 2022. We classified PA as severe when presenting with an altered level of consciousness (Glasgow Coma Scale (GCS) < 15) or visual involvement. RESULTS: A total of 71 PA cases were identified, of whom 80.28% (n = 57) were classified as severe PA. The median age was 60 (18 to 85 years old) and 67.6% (n = 48) were male. Most patients had macroadenomas, except for one patient with a microadenoma of 9 mm. Headache was the most common presenting symptom (90.1%) and anticoagulation was the most frequent predisposing risk factor, but it was not associated with a higher risk for severe PA (odds ratio [OR] 1.13 [0.21-5.90]). Severe cases were associated with male gender (OR 5.53 [1.59-19.27]), tumor size >20 mm (OR 17.67 [4.07-76.64]), and Knosp grade ≥2 (OR 9.6 [2.38-38.73]). In the multivariant analysis, the only variables associated with a higher risk for severe PA were tumor size and Knosp grade. Surgery was more common in severe PA than in non-severe (91.2% vs. 64.3%, P = 0.009). CONCLUSION: A tumor size >20 mm and cavernous sinus invasion are risk factors for developing a severe PA. These risk factors can stratify patients at a higher risk of a worse clinical picture, and subsequently, more need of decompressive surgery.
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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/tratamento farmacológico , Acromegalia/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Cabergolina/uso terapêutico , Resultado do Tratamento , Prolactina/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Hormônio do Crescimento Humano , Adenoma/tratamento farmacológico , Adenoma/sangue , Adenoma/metabolismo , Adenoma/complicações , Idoso , Quimioterapia Combinada , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/complicações , Espanha/epidemiologiaRESUMO
INTRODUCTION: Growth hormone (GH)-secreting pituitary tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display cavernous sinus invasion. Biomarker assessment associated with tumor growth and invasion is important to optimize their management. OBJECTIVES: The study aims to identify clinical/hormonal/molecular biomarkers associated with tumor size and invasiveness in GHomas and to analyze the influence of pre-treatment with somatostatin analogs (SSAs) or dopamine agonists (DAs) in key molecular biomarker expression. METHODS: Clinical/analytical/radiological variables were evaluated in 192 patients from the REMAH study (ambispective multicenter post-surgery study of the Spanish Society of Endocrinology and Nutrition). The expression of somatostatin/ghrelin/dopamine system components and key pituitary/proliferation markers was evaluated in GHomas after the first surgery. Univariate/multivariate regression studies were performed to identify association between variables. RESULTS: Eighty percent of patients harbor macroadenomas (63.8% with extrasellar growth). Associations between larger and more invasive GHomas with younger age, visual abnormalities, higher IGF1 levels, extrasellar/suprasellar growth, and/or cavernous sinus invasion were found. Higher GH1 and lower PRL/POMC/CGA/AVPR1B/DRD2T/DRD2L expression levels (P < .05) were associated with tumor invasiveness. Least Absolute Shrinkage and Selection Operator's penalized regression identified combinations of clinical and molecular features with areas under the curve between 0.67 and 0.82. Pre-operative therapy with DA or SSAs did not alter the expression of any of the markers analyzed except for DRD1/AVPR1B (up-regulated with DA) and FSHB/CRHR1 (down-regulated with SSAs). CONCLUSIONS: A specific combination of clinical/analytical/molecular variables was found to be associated with tumor invasiveness and growth capacity in GHomas. Pre-treatment with first-line drugs for acromegaly did not significantly modify the expression of the most relevant biomarkers in our association model. These findings provide valuable insights for risk stratification and personalized management of GHomas.
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Acromegalia , Adenoma , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Invasividade Neoplásica , Humanos , Masculino , Feminino , Acromegalia/metabolismo , Pessoa de Meia-Idade , Adulto , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma/metabolismo , Adenoma/patologia , Idoso , Agonistas de Dopamina/uso terapêutico , Biomarcadores Tumorais/metabolismo , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Hormônio do Crescimento Humano/metabolismoRESUMO
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 , Hormônio do Crescimento Humano , Tumores Neuroendócrinos , Prolactina , Somatostatina , Humanos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Masculino , Feminino , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Pessoa de Meia-Idade , Adulto , Prolactina/sangue , Prolactina/metabolismo , Estudos Retrospectivos , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/metabolismo , Acromegalia/tratamento farmacológico , Acromegalia/metabolismo , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/metabolismo , Idoso , Adulto JovemRESUMO
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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BACKGROUND AND OBJECTIVE: Nodal metastases in the central compartment are frequent in papillary thyroid cancer (PTC). However, they are mostly micrometastases with no impact on survival and their relevance on the risk of locoregional relapse is controversial. There is no consensus regarding optimal management of the central neck in patients with PTC cN0. In our center, we do not perform prophylactic central neck dissection (pCND). The objective of this study is to review our long-term results and compare them with the most recent literature. PATIENTS AND METHODS: Retrospective review of patients with PTC who underwent total thyroidectomy (TT) without CND between 2005 and 2017. Primary result was disease-free survival in the neck (DFS). RESULTS: 321 patients were identified, mostly T1-T2 tumors (94.1%). Median follow-up was 90 months. DFS in the central compartment was excellent (96.1% at 10 year's follow-up). 19 patients had cervical recurrence, of which 15 underwent salvage surgery. On their last visit, including salvage surgery when appropriate, 77% of patients had excellent response, 18.7% had indeterminate response, 3.1% had biochemically incomplete response and 1.2% had morphologically incomplete response. Recurrent laryngeal nerve (RLN) paralysis after TT was transient in 4.7% of patients and permanent in 0.9% of patients. There were no RLN paralysis after salvage surgery. Permanent hypoparathyroidism occurred in 3.4% of patients. Only one patient had hypoparathyroidism after salvage surgery and it was permanent. CONCLUSIONS: Based on long-term results and low rate of complications associated with salvage surgery in our experience, we consider routine pCND is not justified.
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Esvaziamento Cervical , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Estudos Retrospectivos , Masculino , Feminino , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Pessoa de Meia-Idade , Adulto , Câncer Papilífero da Tireoide/cirurgia , Tireoidectomia/métodos , Idoso , Intervalo Livre de Doença , Recidiva Local de Neoplasia , Adulto Jovem , Metástase Linfática , Resultado do Tratamento , Adolescente , Terapia de Salvação , Idoso de 80 Anos ou mais , Carcinoma Papilar/cirurgiaRESUMO
PURPOSE: To identify presurgical and surgical risk factors for intraoperative hypertensive crisis in patients with pheochromocytomas and sympathetic paragangliomas (PGLs) (PPGLs). METHODS: Retrospective multicenter cohort study of patients with PPGLs from 18 tertiary hospitals. Intraoperative hypertensive crisis was defined as systolic blood pressure (SBP) greater than 200âmmHg lasting more than 1âmin and postoperative hypertensive crisis as SBP greater than 180âmmHg or diastolic blood pressure (DBP) greater than 110âmmHg. RESULTS: A total of 296 surgeries were included. Alpha presurgical blockade was employed in 93.2% of the cases and beta-adrenergic in 53.4%. Hypertensive crisis occurred in 20.3% ( n â=â60) of the surgeries: intraoperative crisis in 56 and postoperative crisis in 6 cases (2 cases had both types of crises). We identified as risk factors of intraoperative hypertensive crisis, absence of presurgical glucocorticoid therapy (odds ratio [OR] 3.48; 95% confidence interval [CI] 1.19-10.12) higher presurgical SBP (OR 1.22 per each 10âmmHg, 95% CI 1.03-1.45), a larger tumor size (OR 1.09 per each 10âmm, 95% CI 1.00-1.19) and absence of oral sodium repletion (OR 2.59, 95% CI 1.25-5.35). Patients with hypertensive crisis had a higher rate of intraoperative bleeding ( P â<â0.001), of intraoperative hemodynamic instability ( P â<â0.001) and of intraoperative hypotensive episodes ( P â<â0.001) than those without hypertensive crisis. CONCLUSION: Intraoperative hypertensive crisis occurs in up to 20% of the PPGL resections. Patients not pretreated with glucocorticoid therapy before surgery, with larger tumors and higher presurgical SBP and who do not receive oral sodium repletion have a higher risk for developing hypertensive crisis during and after PPGL surgery.
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Neoplasias das Glândulas Suprarrenais , Hipertensão , Crise Hipertensiva , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/complicações , Feocromocitoma/cirurgia , Feocromocitoma/patologia , Hipertensão/epidemiologia , Estudos de Coortes , Glucocorticoides , Pressão Sanguínea/fisiologia , Paraganglioma/complicações , Paraganglioma/cirurgia , Fatores de Risco , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia , Sódio , Estudos RetrospectivosRESUMO
Purpose: To evaluate the rate of recurrence among patients with pheochromocytomas and sympathetic paragangliomas (PGLs; together PPGLs) and to identify predictors of recurrence (local recurrence and/or metastatic disease). Methods: This retrospective multicenter study included information of 303 patients with PPGLs in follow-up in 19 Spanish tertiary hospitals. Recurrent disease was defined by the development of local recurrence and/or metastatic disease after initial complete surgical resection. Results: A total of 303 patients with PPGLs that underwent 311 resections were included (288 pheochromocytomas and 15 sympathetic PGLs). After a median follow-up of 4.8 years (range 1-19), 24 patients (7.9%) had recurrent disease (3 local recurrence, 17 metastatic disease and 4 local recurrence followed by metastatic disease). The median time from the diagnosis of the PPGL to the recurrence was of 11.2 months (range 0.5-174) and recurrent disease cases distributed uniformly during the follow-up period. The presence of a pathogenic variant in SDHB gene (hazard ratio [HR] 13.3, 95% CI 4.20-41.92), higher urinary normetanephrine levels (HR 1.02 per each increase in standard deviation, 95% CI 1.01-1.03) and a larger tumor size (HR 1.01 per each increase in mm, 95% CI 1.00-1.02) were independently associated with disease recurrence. Conclusion: The recurrence of PPGLs occurred more frequently in patients with SDHB mutations, with larger tumors and with higher urinary normetanephrine levels. Since PPGL recurrence may occur at any time after the initial PPGL diagnosis is performed, we recommend performing a strict follow-up in all patients with PPGLs, especially in those patients with a higher risk of recurrent disease.
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Neoplasias das Glândulas Suprarrenais , Neoplasias Encefálicas , Segunda Neoplasia Primária , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/patologia , Normetanefrina , Recidiva Local de Neoplasia , Paraganglioma/patologia , Neoplasias das Glândulas Suprarrenais/diagnósticoRESUMO
Introduction: We previously described that a short version of the acute octreotide test (sAOT) can predict the response to first-generation somatostatin receptor ligands (SRLs) in patients with acromegaly. We have prospectively reassessed the sAOT in patients from the ACROFAST study using current ultra-sensitive GH assays. We also studied the correlation of sAOT with tumor expression of E-cadherin and somatostatin receptor 2 (SSTR2) . Methods: A total of 47 patients treated with SRLs for 6 months were evaluated with the sAOT at diagnosis and correlated with SRLs' response. Those patients whose IGF1 decreased to <3SDS from normal value were considered responders and those whose IGF1 was ≥3SDS, were considered non-responders. The 2 hours GH value (GH2h) after s.c. administration of 100 mcg of octreotide was used to define predictive cutoffs. E-cadherin and SSTR2 immunostaining in somatotropinoma tissue were investigated in 24/47 and 18/47 patients, respectively. Results: In all, 30 patients were responders and 17 were non-responders. GH2h was 0.68 (0.25-1.98) ng/mL in responders vs 2.35 (1.59-9.37) ng/mL in non-responders (p<0.001). GH2h = 1.4ng/mL showed the highest ability to identify responders (accuracy of 81%, sensitivity of 73.3%, and specificity of 94.1%). GH2h = 4.3ng/mL was the best cutoff for non-response prediction (accuracy of 74%, sensitivity of 35.3%, and specificity of 96.7%). Patients with E-cadherin-positive tumors showed a lower GH2h than those with E-cadherin-negative tumors [0.9 (0.3-2.1) vs 3.3 (1.5-12.1) ng/mL; p<0.01], and patients with positive E-cadherin presented a higher score of SSTR2 (7.5 ± 4.2 vs 3.3 ± 2.1; p=0.01). Conclusion: The sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly.
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Acromegalia , Adenoma , Neoplasias Hipofisárias , Humanos , Octreotida/uso terapêutico , Acromegalia/diagnóstico , Acromegalia/tratamento farmacológico , Acromegalia/metabolismo , Somatostatina/uso terapêutico , Resultado do Tratamento , Neoplasias Hipofisárias/metabolismo , Adenoma/tratamento farmacológico , CaderinasRESUMO
PURPOSE: to perform an external validation of our predictive model to rule out pheochromocytoma (PHEO) based on unenhanced CT in a cohort of patients with PHEOs and adenomas who underwent adrenalectomy. METHODS: The predictive model was previously developed in a retrospective cohort of 1131 patients presenting with adrenal lesions. In the present study, we performed an external validation of the model in another cohort of 214 patients with available histopathological results. RESULTS: For the external validation, 115 patients with PHEOs and 99 with adenomas were included. Our previously described predictive model combining the variables of high lipid content and tumor size in unenhanced CT (AUC-ROC: 0.961) had a lower diagnostic accuracy in our current study population for the prediction of PHEO (AUC: 0.750). However, when we excluded atypical adenomas (with Hounsfield units (HU) > 10, n = 39), the diagnostic accuracy increased to 87.4%. In addition, in the whole cohort (including atypical adenomas), when MRI information was included in the model, the diagnostic accuracy increased to up to 85% when the variables tumor size, high lipid content in an unenhanced CT scan, and hyperintensity in the T2 sequence in MRI were included. The probability of PHEO was <0.3% for adrenal lesions <20 mm with >10 HU and without hyperintensity in T2. CONCLUSION: Our study confirms that our predictive model combining tumor size and lipid content has high reliability for the prediction of PHEO when atypical adrenal lesions are excluded. However, for atypical adrenal lesions with >10 HU in an unenhanced CT scan, MRI information is necessary for a proper exclusion of the PHEO diagnosis.
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OBJECTIVE: Acromegaly is a rare disease caused by increased growth hormone secretion and a subsequent increase in insulin-like growth factor I (IGF-I) levels. Patients display multiple comorbidities that affect their quality of life (QoL). Treatment aims to maintain good biochemical control, tumour control and reduce the risk of comorbidities; however, their impact on QoL has been overlooked until recently. We interviewed patients to explore their preferences with regard to treatment attributes. DESIGN: A cross-sectional study based on interviews and a discrete choice experiment (DCE) in a Spanish cohort. METHODS: Adult patients diagnosed with acromegaly ≥1 year before the start of the study and under treatment were included. Treatment attributes were collected from patient testimony during face-to-face interviews. Then, a DCE was performed to elicit patient preferences for certain treatment attributes. RESULTS: Sixty-seven patients completed the study. QoL improvement was the most important treatment attribute (37%), followed by IGF-I control (20%), blood sugar control (17%) and tumour control (13%). Secondary attributes were pain associated with the route of administration (7%), diarrhoea (2%), administration method (2%) and storage conditions (2%). We then calculated the theoretical share of preference for existing treatments, based on the individual preference utility for each attribute and level. Pegvisomant obtained the highest share of preference overall, and the highest preference as a second-line treatment (53 and 95%, respectively). CONCLUSIONS: QoL greatly influences patient treatment preference. Since acromegaly patients are informed and aware of their disease, treatment choices should always be shared with patients.
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Acromegalia , Qualidade de Vida , Adulto , Humanos , Fator de Crescimento Insulin-Like I , Acromegalia/tratamento farmacológico , Espanha , Estudos Transversais , Preferência do PacienteRESUMO
PURPOSE: To compare the clinical, hormonal, and radiological presentation and surgical outcomes of patients with macroadenomas presenting with pituitary apoplexy and patients not presenting pituitary apoplexy. METHODS: Multicentre retrospective study of patients presenting with macroadenomas and pituitary apoplexy in three Spanish tertiary hospitals between 2008 and 2022. We selected as control group (non-pituitary apoplexy), patients with pituitary macroadenomas without apoplexy who underwent pituitary surgery between 2008 and 2020. RESULTS: A total of 60 patients with apoplexy and 185 without apoplexy were enrolled. Patients with pituitary apoplexy were more frequently men (70% vs. 48.1%, p = 0.003), had higher prevalence of hypertension (43.3% vs. 26.0%, p = 0.011) and of obesity (23.3% vs. 9.7%, P = 0.007), were under treatment with anticoagulants more commonly (11.7% vs. 4.3%, P = 0.039) and had larger (27.5 ± 11.03 vs. 23.6 ± 12.55 mm, p = 0.035) and invasive pituitary macroadenomas more frequently (85.7% vs. 44.3%, P < 0.001) than those without apoplexy. Surgical remission was more frequent in patients with pituitary apoplexy than those without apoplexy (OR 4.55, P < 0.001), but they developed new pituitary deficits (OR 13.29, P < 0.001) and permanent diabetes insipidus (OR 3.40, P = 0.022) more commonly. However, visual improvement (OR 6.52, p < 0.001) and complete pituitary function recovery (OR 2.37, P < 0.001) was more common in patients without apoplexy. CONCLUSION: Surgical resection is more common in patients presenting with pituitary apoplexy than those without apoplexy; however, visual improvement and complete recovery of pituitary function is more common in patients without apoplexy. The risk of new pituitary deficits and permanent diabetes insipidus is higher in patients with apoplexy than in those without it.
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Adenoma , Diabetes Insípido , Apoplexia Hipofisária , Neoplasias Hipofisárias , Masculino , Humanos , Estudos Retrospectivos , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Apoplexia Hipofisária/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Resultado do TratamentoRESUMO
CONTEXT: There are no data on mortality of acromegaly diagnosed in older individuals. OBJECTIVE: This work aimed to compare clinical characteristics, growth hormone-related comorbidities, therapeutic approaches, and mortality rate of patients diagnosed before or after 2010 and to assess overall mortality rate compared with the general Spanish population. METHODS: A retrospective evaluation was conducted among Spanish tertiary care centers of 118 patients diagnosed with acromegaly at age 65 or older. Kaplan-Meier curves were constructed to trace survival, and Cox proportional hazard models were used to assess the risk factors associated with mortality. We also compared mortality with that of the Spanish population by using age- and sex-adjusted standardized mortality ratios (SMRs). RESULTS: No differences were found in first-line treatment or biochemical control, between both periods except for faster biochemical control after 2010. Twenty-nine (24.6%) patients died, without differences between groups, and had a median of follow-up 8.6 years (103, [72.3] months). Overall SMR was 1.02 (95% CI, 0.57-1.54), (0.60; 95% CI, 0.35-1.06) for men and (1.80; 95% CI, 1.07-2.94) for women. The most common cause of death was cardiovascular disease (CVD). CONCLUSION: The mortality in patients with acromegaly diagnosed in older individuals was no different between both periods, and there was no overall SMR difference compared with the general Spanish population. However, the SMR was higher in women. As CVD is the leading cause of mortality, it seems advisable to initiate an intense CVD protective treatment as soon as acromegaly is diagnosed, particularly in women, in addition to tight acromegaly control to prevent excess mortality.
Assuntos
Acromegalia , Doenças Cardiovasculares , Hormônio do Crescimento Humano , Masculino , Humanos , Feminino , Idoso , Acromegalia/diagnóstico , Acromegalia/epidemiologia , Acromegalia/tratamento farmacológico , Estudos Retrospectivos , Espanha/epidemiologia , Hormônio do Crescimento Humano/uso terapêutico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológicoRESUMO
The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.
Assuntos
Neoplasias das Glândulas Suprarrenais , Segunda Neoplasia Primária , Paraganglioma , Feocromocitoma , Humanos , Neoplasias das Glândulas Suprarrenais/genética , Genômica , Paraganglioma/genética , Paraganglioma/imunologia , Feocromocitoma/genética , Feocromocitoma/imunologia , Microambiente Tumoral/genéticaRESUMO
INTRODUCTION: It is estimated that 30-40% of patients with apparently sporadic pheochromocytomas (PHEOs) have an inherited predisposition syndrome. The aim of our study was to develop a predictive model of hereditary PHEO based on the clinical, hormonal, and radiological features present at the diagnosis of patients with PHEOs. METHODS: A retrospective multicenter cohort study of patients with PHEOs with available genetic study from 18 tertiary hospitals. Clinical, biochemical, and radiological features were used to build a multivariate logistic regression model. The estimation of all possible equations was used to select the model with the best diagnostic accuracy (lower Akaike index). RESULTS: A total of 245 patients were included: 169 (69.0%) patients with sporadic PHEOs and 76 (31%) with hereditary PHEOs. The parsimonious predictive model with the highest diagnostic accuracy for the prediction of hereditary PHEO combined the variables age, non-cardiovascular disease, urinary norepinephrine levels, and tumor size. The area under the ROC curve of this model was 0.800 (0.705-0.887). Based on the predictive model, the probability of hereditary PHEO in patients older than 60 years with cardiovascular disease, high levels of urinary norepinephrine and unilateral PHEOs >60 mm was <2%. And if the age was above 80 years, lower than 1%. The probability of sporadic PHEO linearly increased with age (MH Test for linear Trend: χ2 (1) = 30.05; p < 0.001). CONCLUSION: In certain populations such as old patients with cardiovascular disease, with high levels of urinary norepinephrine and large tumors in which the probability of hereditary PHEO is very low, genetic testing could be avoided in the absence of specific suspicion.
Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Humanos , Idoso de 80 Anos ou mais , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/patologia , Estudos de Coortes , Testes Genéticos , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , NorepinefrinaRESUMO
OBJECTIVES: To report a rare case of a metastatic adrenocortical carcinoma (ACC) that achieve a complete and a long-term remission. CASE PRESENTATION: AAC is a rare and aggressive tumor, with a high risk of recurrence and that present metastases in 21% of cases at diagnosis. Treatment of advanced ACC is challenging, mitotane is the only available adrenolytic treatment, with modest and unpredictable responses. Response rates to systemic chemotherapy are not encouraging. We describe the case of a 39-year-old woman with a metastatic ACC, that achieve a complete and long-term remission after chemotherapy, mitotane treatment and surgery of primary tumor and liver metastases. CONCLUSIONS: A complete remission of a metastatic adrenocortical carcinoma is possible in some rare cases after a multimodal treatment.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Feminino , Humanos , Adulto , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/patologia , Mitotano/uso terapêutico , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/patologia , Antineoplásicos Hormonais/uso terapêutico , Terapia CombinadaRESUMO
Context: Some reports suggest that acromegaly in elderly patients has a more benign clinical behavior and could have a better response to first-generation long-acting somatostatin receptor ligands (SRL). However, there is no specific therapeutic protocol for this special subgroup of patients. Objective: This study aimed at identifying predictors of response to SRL in elderly patients. Design: Multicentric retrospective nationwide study of patients diagnosed with acromegaly at or over the age of 65 years. Results: One-hundred and eighteen patients (34 men, 84 women, mean age at diagnosis 71.7 ± 5.4 years old) were included. Basal insulin-like growth factor type 1 (IGF-1) above the upper limit of normal (ULN) and growth hormone (GH) levels (mean ± SD) were 2.7 ± 1.4 and 11.0 ± 11.9 ng/ml, respectively. The mean maximal tumor diameter was 12.3 ± 6.4 mm, and up to 68.6% were macroadenoma. Seventy-two out of 118 patients (61.0%) underwent surgery as primary treatment. One-third of patients required first-line medical treatment due to a rejection of surgical treatment or non-suitability because of high surgical risk. After first-line surgery, 45/72 (63.9%) were in disease remission, and 16/34 (46.7%) of those treated with SRL had controlled disease. Patients with basal GH at diagnosis ≤6 ng/ml had lower IGF-1 levels and had smaller tumors, and more patients in this group reached control with SRL (72.7% vs. 33.3%; p < 0.04) [OR: 21.3, IC: 95% (2.4-91.1)], while male patients had a worse response [OR: 0.09, IC 95% (0.01-0.75)]. The predictive model curve obtained for SRL response showed an AUC of 0.82 CI (0.71-0.94). Conclusions: The most frequent phenotype in newly diagnosed acromegaly in the elderly includes small adenomas and moderately high IGF-1 levels. GH at diagnosis ≤6 ng/ml and female gender, but not age per se, were associated with a greater chance of response to SRL.