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1.
Artículo en Inglés | MEDLINE | ID: mdl-38818709

RESUMEN

OBJECTIVE: To report our experience with 18F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRICR) in the care trajectory for persistent acromegaly. DESIGN: Prospective case series. PATIENTS: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options. MEASUREMENTS: FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery. RESULTS: FET-PET/MRICR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET-PET/MRICR was fully concordant with conventional MRI, and in one patient partially concordant. FET-PET/MRICR identified suggestive new foci in four other patients. Surgical re-exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRICR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF-1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients. CONCLUSIONS: In patients with persisting acromegaly without a clear surgical target on MRI, FET-PET/MRICR is a new tracer to provide additional information to aid decision-making by the multidisciplinary pituitary team.

2.
Pituitary ; 26(3): 307-317, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37014498

RESUMEN

PURPOSE: To describe quality and outcomes of patient-reported outcome (PRO) measures (PROMs) used in patients with refractory hormone-producing pituitary adenomas, and to provide an overview of PROs in these challenging pituitary adenomas. METHODS: Three databases were searched for studies reporting on refractory pituitary adenomas. For the purpose of this review, refractory adenomas were defined as tumors resistant to primary therapy. General risk of bias was assessed using a component approach and the quality of PROM reporting was assessed using the International Society for Quality of Life Research (ISOQOL) criteria. RESULTS: 20 studies reported on PROMs in refractory pituitary adenomas, using 14 different PROMs, of which 4 were disease specific (median general risk of bias score: 33.5% (range 6-50%) and ISOQOL score: 46% (range 29-62%)). SF-36/RAND-36 and AcroQoL were most frequently used. Health-related quality of life in refractory patients (measured by AcroQoL, SF-36/Rand-36, Tuebingen CD-25, and EQ-5D-5L) varied greatly across studies, and was not always impaired compared to patients in remission. CONCLUSION: There is a scarcity of data on PROs in the subset of pituitary adenomas that is more difficult to treat, e.g., refractory and these patients are difficult to isolate from the total cohort. The patients' perspective on quality of life, therefore, remains largely unknown in refractory patients. Thus, PROs in refractory pituitary adenomas require adequate analysis using properly reported disease specific PROMs in large cohorts to enable appropriate interpretation for use in clinical practice.


Asunto(s)
Adenoma , Neoplasias Hipofisarias , Humanos , Calidad de Vida , Medición de Resultados Informados por el Paciente , Hormonas
3.
Pituitary ; 26(5): 611-621, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37690076

RESUMEN

PURPOSE: To describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery. METHODS: Retrospective observational cohort study of consecutive patients with prolactinoma undergoing surgery from 2017 to 2019 at the referral center (RC), prior to surgery being considered a viable treatment option (i.e. PRolaCT study). Demographics and clinical data (type and duration of pretreatment and surgical indications, goals, and outcomes) were collected from patient records. Care trajectories were divided into three phases: (1) diagnosis and initial treatment, (2) endocrine treatment at the RC, and (3) surgical treatment. RESULTS: 40 patients were included (31 females (77.5%), median age 26.5 (14-63) years. Indications for surgery were dopamine agonist (DA) intolerance (n = 31, 77.5%), resistance (n = 6, 15.0%), and patient/physician preference (n = 3, 7.5%). Patients were pretreated with DA (n = 39 (97.5%)), and surgery (n = 3 (7.5%)). Median disease duration at surgery was 4 (0-27) years. Primary surgical goal was total resection in 38 patients (95.0%), of which biochemical remission was achieved 6 months postoperatively in 23 patients (62.2%), and clinical remission in 6 patients (16.2%), missing data n = 1. CONCLUSION: Care trajectories were highly individualized based on patient and tumor characteristics, as well as the multidisciplinary team's assessment (need for alternative treatment, surgical chances and risks). Most patients were pretreated pharmacologically and had broad variation in timing of referral, undergoing surgery as last-resort treatment predominantly due to DA intolerance. High quality imaging and multidisciplinary consultations with experienced neurosurgeons and endocrinologists enabling treatment tailored to patients' needs were prerequisites for adequate counseling in treatment of patients with prolactinoma.


Asunto(s)
Neoplasias Hipofisarias , Prolactinoma , Femenino , Humanos , Adulto , Prolactinoma/tratamiento farmacológico , Prolactinoma/cirugía , Prolactinoma/patología , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Estudios Retrospectivos , Resultado del Tratamiento , Agonistas de Dopamina/uso terapéutico , Prolactina
4.
J Neuroophthalmol ; 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37669254

RESUMEN

BACKGROUND: This retrospective, observational cohort study aimed to determine recovery rate and recovery time of ocular motor nerve palsies (OMP) of third (CN III), fourth (CN IV), or sixth cranial nerves (CN VI)-and associated prognostic factors-in meningioma and pituitary adenoma (PA) patients. METHODS: A total of 25 meningioma (28 eyes) and 33 PA patients (36 eyes), treated at the Leiden University Medical Center in the Netherlands from January 1, 1978 to January 31, 2021, were included. OMPs were evaluated according to a newly created recovery scale using on-clinical and orthoptic examinations, which were performed every 3-4 months until palsy recovery, or at 18 months follow-up. RESULTS: Recovery rates of CN III (meningioma 23.5% vs PA 92.3%), CN IV (meningioma 20% vs PA 100%), and CN VI (meningioma 60% vs PA 100%) palsies were observed at 18 months follow-up, with differences between the 2 tumor types being observed in the treated patients only. Median recovery time of all OMPs combined was significantly longer in meningioma patients (37.9 ± 14.3 months vs 3.3 ± 0.1 months; P < 0.001). No significant protective or risk factors for recovery rate or time were identified. CONCLUSIONS: OMP recovery rates in treated patients were more favorable in patients with PA compared with patients with meningiomas, independent of OMP cause. With these new insights in OMP recovery, more accurate prognoses and appropriate follow-up strategies can be determined for meningioma and PA patients with OMPs.

5.
Pituitary ; 25(4): 622-635, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35726113

RESUMEN

PURPOSE: Acromegalic arthropathy is a well-known phenomenon, occurring in most patients regardless of disease status. To date, solely hips, knees, hands, and spinal joints have been radiographically assessed. Therefore, this study aimed to assess the prevalence of joint symptoms and radiographic osteoarthritis (OA) of new, and established peripheral joint sites in well-controlled acromegaly. METHODS: Fifty-one acromegaly patients (56% female, mean age 64 ± 12 years) in long-term remission for 18.3 years (median, IQR 7.2-25.4) were included. Nineteen patients currently received pharmacological treatment. Self-reported joint complaints were assessed using standardized interviews. Self-reported disability of the upper and lower limbs, and health-related quality of life (HR-QoL) were evaluated using validated questionnaires. Radiographic OA [defined as Kellgren & Lawrence (KL) ≥ 2] was scored using (modified) KL methods. RESULTS: Radiographic signs of OA were present in 46 patients (90.2%) with ≥ 2 joints affected in virtually all of these patients (N = 44; 95.7%). Radiographic MTP1 OA was as prevalent as radiographic knee OA (N = 26, 51.0%), and radiographic glenohumeral OA was similarly prevalent as hip OA [N = 21 (41.2%) vs. N = 24 (47.1%)]. Risk factors for radiographic glenohumeral OA were higher pre-treatment IGF-1 levels [OR 1.06 (1.01-1.12), P = 0.021], and current pharmacological treatment [OR 5.01 (1.03-24.54), P = 0.047], whereas no risk factors for MTP1 joint OA could be identified. CONCLUSION: Similar to previously-assessed peripheral joints, clinical and radiographic arthropathy of the shoulder and feet were prevalent in controlled acromegaly. Further studies on adequate management strategies of acromegalic arthropathy are needed.


Asunto(s)
Acromegalia , Osteoartritis de la Cadera , Osteoartritis de la Rodilla , Acromegalia/diagnóstico por imagen , Acromegalia/terapia , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Rodilla/epidemiología , Prevalencia , Calidad de Vida
6.
Pituitary ; 25(2): 229-237, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34687408

RESUMEN

PURPOSE: Pain is a common symptom of acromegaly, impairing health-related quality of life (HR-QoL) significantly despite long-term disease remission. Neuropathic-like pain (NP-like) symptoms are invalidating, with great impact on HR-QoL. Studies characterizing or investigating the etiology of pain in acromegaly are scarce. Therefore, we aimed to assess NP-like symptoms in a cohort of controlled acromegaly patients. METHODS: Forty-four long-term controlled acromegaly patients (aged 62.6 ± 12.6 years; 56.8% female) were included in this cross-sectional study. NP-like symptoms were assessed using the validated painDETECT questionnaire. Patients were divided in three probability-based NP-like symptoms categories based on the total score (range 0-35): unlikely (≤ 12), indeterminate (13-18) and likely (≥ 19). HR-QoL (physical component score (PCS), and mental component score (MCS)), and self-reported pain were assessed using Short Form-36 (SF-36). Potential risk factors were determined using linear regression analyses. RESULTS: Self-reported pain was reported by 35 patients (79.5%). Likely NP-like symptoms were present in 4/44 patients (9.1%), and indeterminate NP-like symptoms in 6/44 patients (13.6%). All patients with likely NP-like symptoms were female. Higher painDETECT scores were negatively associated with HR-QoL (PCS: r = - 0.46, P = 0.003; MCS: r = - 0.37, P = 0.018), and SF-36 pain scores (r = - 0.63, P < 0.0001). Female sex was a risk factor for NP-like symptoms. CONCLUSIONS: Pain was prevalent in controlled acromegaly patients, whereas NP-like symptoms were relatively infrequent, and only observed in females. NP-like symptoms were associated with lower HR-QoL in acromegaly. Since specific analgesic therapy is available, awareness for characterization, increased understanding, and clinical trials regarding neuropathic pain identification and treatment in acromegaly patients are warranted.


Asunto(s)
Acromegalia , Calidad de Vida , Acromegalia/epidemiología , Acromegalia/terapia , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor , Prevalencia , Encuestas y Cuestionarios
7.
Pituitary ; 24(1): 68-78, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33057947

RESUMEN

PURPOSE: To evaluate whether the occurrence of chiasmal herniation coincides with visual field (VF) deterioration and to compare the course of VF defects in patients with and without radiological chiasmal herniation following treatment of pituitary adenoma. METHODS: This retrospective cohort study included 48 pituitary macroadenoma patients with chiasm compression, divided into three groups: Group 1 (N = 12), downward displaced optic chiasm and deteriorated VFs; Group 2 (N = 16), downward displaced optic chiasm; Group 3 (N = 20), control-group matched for tumour size and follow-up VFs, in mean deviation (dB). VFs were compared over time and a severity index, Chiasm Herniation Scale (CHS), for herniation based on radiological parameters was designed. RESULTS: After treatment, all groups showed improvement of VFs (Gr1: 2.97 dB p = 0.097, Gr2: 4.52 dB p = 0.001 and Gr3: 5.16 dB p = 0.000), followed by long-term gradual deterioration. The course of VFs between patients with and without herniation was not significantly different (p = 0.143), neither was there a difference in the course before and after herniation (p = 0.297). The median time till onset of herniation was 40 months (IQR 6 month-10 years) and did not significantly differ (p = 0.172) between the groups. There was no relation between VFs and the degree of herniation (p = 0.729). CONCLUSION: Herniation does not appear to have clinical relevance with respect to VF outcome. The newly designed CHS is the first scoring system to quantify the severity of herniation and, in the absence of alternatives, may be useful to describe MRI findings to serve future added value in larger sized outcome studies.


Asunto(s)
Neoplasias Hipofisarias/metabolismo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quiasma Óptico/metabolismo , Neoplasias Hipofisarias/genética , Estudios Retrospectivos , Campos Visuales/fisiología
8.
Pituitary ; 23(4): 417-429, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32419072

RESUMEN

PURPOSE: Surgery in patients with non-functioning pituitary macroadenomas (NFMA) is effective in ameliorating visual function. The urgency for decompression, and preferred timing of surgery related to the preoperative severity of dysfunction is unknown. METHODS: Systematic review for evidence to provide clinical guidance for timing of surgical decompression of the optic chiasm, and a cohort study of 30 NFMA patients, in whom mean deviation (MD), and severity of visual dysfunction was assessed. RESULTS: Systematic review 44 studies were included with a total of 4789 patients. Postoperatively, visual field defects improved in 87.0% of patients, stabilized in 12.8% and worsened in 1.0%. Specific protocols regarding timing of surgery were not reported. Only seven studies (16.7%) reported on either the duration of visual symptoms, or diagnostic, or treatment delay. Cohort study 30 NFMA patients (50% female, 60 eyes, mean age 58.5 ± 14.8 years), had a median MD of - 5.3 decibel (IQR - 3.1 to - 10.1). MD was strongly correlated with clinical severity (r = - 0.94, P < 0.0001), and were used for severity of defects cut-off values: (1) normal > - 2 dB, (2) mild - 2 dB to - 4 dB, (3) moderate - 4 to - 8 dB, (4) severe - 8 to - 17 dB, (5) very severe < - 17 dB. CONCLUSION: Surgical decompression is highly effective in improving visual function. Uniform, quantitative grading of visual dysfunction was lacking. MD is a promising quantitative outcome measure. We provide recommendations for the evaluation of timing of surgery, considering severity of visual impairment, which will need further validation based on expert clinical practice.


Asunto(s)
Adenoma/cirugía , Hemianopsia/fisiopatología , Neoplasias Hipofisarias/cirugía , Calidad de la Atención de Salud , Recuperación de la Función , Adenoma/complicaciones , Adenoma/patología , Adenoma/fisiopatología , Estudios de Cohortes , Descompresión Quirúrgica , Femenino , Hemianopsia/etiología , Humanos , Masculino , Persona de Mediana Edad , Quiasma Óptico , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/fisiopatología , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral , Trastornos de la Visión/etiología , Trastornos de la Visión/fisiopatología , Agudeza Visual , Pruebas del Campo Visual
9.
Pituitary ; 23(4): 430-431, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32567033

RESUMEN

The original version of the article unfortunately contained an error in Figure 2. The term 'Refer within 3 days' should read 'Refer as soon as possible'. Corrected version of Figure 2 is given below.

10.
J Pediatr Hematol Oncol ; 40(2): e64-e68, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29016413

RESUMEN

Central venous catheters (CVCs) in neonates are associated with an increased risk of thrombosis. Most reports focus on umbilical venous catheters (UVCs) and peripherally inserted central catheters (PICCs), whereas data available on femoral venous catheters (FVCs) are limited. We performed a retrospective cohort study in all neonates (gestational age ≥34 wk) with CVCs. The primary outcome was the occurrence of thrombosis in CVCs. The secondary outcomes were possible risk factors for thrombosis, the thrombotic incidence in FVCs, UVCs, and PICCs, and clinical aspects of thrombosis in these groups. A total of 552 neonates received a total of 656 catheters, including 407 (62%) UVCs, 185 (28%) PICCs, and 64 (10%) FVCs. Thrombosis was detected in 14 cases, yielding an overall incidence of 2.1% or 3.6 events per 1000 catheter days. FVC was significantly associated with the occurrence of thrombosis when compared with UVC (P=0.02; odds ratio, 3.8; 95% confidence interval, 1.2-12.0) and PICC (P=0.01; odds ratio, 8.2; 95% confidence interval, 1.6-41.7). The incidence of thrombosis was higher in FVCs than in UVCs and PICCS, that is, 7.8% (5/64), 1.7% (7/407), and 1.1% (2/185), respectively (P<0.01). The number of thrombotic events per 1000 catheter days was 12.3 in FVCs, 3.2 in UVCs, and 1.5 in PICCs (P<0.05). We concluded that thrombosis occurs more frequently in FVCs than in other CVCs.


Asunto(s)
Cateterismo Venoso Central/efectos adversos , Vena Femoral , Trombosis Venosa Profunda de la Extremidad Superior/epidemiología , Cateterismo Periférico/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Incidencia , Recién Nacido , Masculino , Estudios Retrospectivos , Factores de Riesgo , Venas Umbilicales , Trombosis Venosa Profunda de la Extremidad Superior/etiología
12.
Endocr Connect ; 12(2)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36524809

RESUMEN

Rare endocrine conditions present specific diagnostic and management challenges for healthcare providers, one of which is the understudied transition of care. Despite the need for guidance regarding transition, consensus on structured and protocolled approaches is lacking. Therefore, we aimed to map the current clinical practice and identify unmet needs regarding transition of care for patients with pituitary disease in the reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN). A survey-based, cross-sectional study using the EU Survey tool was performed and completed by 46 physicians (n) from 30 RCs (N). Transition is a common practice among RCs (n = 44/46), usually accomplished by a multidisciplinary team meeting (N = 20/30). Criteria for start and end of transition were defined in half of the RCs, with 16.7% of centers providing dissimilar answers. Transition readiness was assessed by >75% of the RCs, mostly by unvalidated means (e.g. subjective opinions, informal consultations). Pituitary-specific transition assessment tool was applied in one RC only. Transition protocols were present in only 9% of RCs, while in many RCs, transition decisions were taken in combined adult-pediatric meetings or based on clinicians' personal judgment. A minority of physicians evaluated the effectiveness of transition-related interventions (n = 11/46) or medical outcomes (n = 8/46). Patient-reported outcome measures were infrequently used (n = 4/46). Identified unmet needs included the development of guidelines (n = 5/46) and EU-wide approach (n = 2/46). This study exemplifies the unmet needs for a structural definition of the transition period and transition management for patients with rare hypothalamic and pituitary conditions from healthcare providers' perspective.

13.
Arch Med Res ; 54(8): 102918, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38007381

RESUMEN

BACKGROUND: Growth-hormone-producing pituitary adenomas have variable likelihood for biochemical remission (BR). During preoperative counseling, individual estimated surgical likelihoods/risks should be balanced against alternative (medical) treatments, which is necessary for accurate outcome presentation. Preoperative estimation of BR or total resection (TR) likelihoods have not been reported, resulting in extrapolation of individual outcomes. AIMS: To share an innovative outcome reporting paradigm by integrating surgical decision-making, and expected/realized results, resulting from the Value-Based Health Care (VBHC) care path with periodical performance evaluation and care innovation cycle. METHODS: Prospective cohort study of consecutive patients with acromegaly undergoing surgery (January 2016-December 2020; postoperative follow-up ≥6 months) reporting on both classic, and novel innovative outcome evaluations. RESULTS: Fifty eight patients (66 procedures) were included. Intended TR was achieved in 34/50 procedures, whereas intended debulking was achieved in 15/16 procedures. 38/66 procedures resulted in BR, and 4 procedures resulted in permanent complications. Achieving intended surgical goal was estimated preoperatively as likely in 33 (goal achieved (GA) in 28/33), potentially in 27 (GA in 19/27), and unlikely in 6 procedures (GA in 2/6). Integrated Outcome Square 1 (IOQ1) -intended effect achieved without complications- was achieved in 46/66 patients. CONCLUSION: Implementation of the developed quality process positively affects preoperative individual shared decision-making, resulting in improved (individual) outcomes, particularly in complex patients for whom preoperative chances are not fully reflected by tumor size and KNOSP grade, e.g., reoperations, or other challenging circumstances identified during preoperative counseling. Through repeated evaluations, our own team's knowledge increased, allowing for improved individualized treatment strategies.


Asunto(s)
Acromegalia , Adenoma , Adenoma Hipofisario Secretor de Hormona del Crecimiento , Neoplasias Hipofisarias , Humanos , Acromegalia/cirugía , Adenoma/complicaciones , Adenoma/cirugía , Adenoma/patología , Estudios Prospectivos , Resultado del Tratamiento , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , Adenoma Hipofisario Secretor de Hormona del Crecimiento/cirugía , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , Estudios Retrospectivos
14.
Eur J Endocrinol ; 189(1): G1-G42, 2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37318239

RESUMEN

Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas but may also require therapeutic intervention including that for adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma, or metastases. Here, we provide a revision of the first international, interdisciplinary guidelines on incidentalomas. We followed the Grading of Recommendations Assessment, Development and Evaluation system and updated systematic reviews on 4 predefined clinical questions crucial for the management of incidentalomas: (1) How to assess risk of malignancy?; (2) How to define and manage mild autonomous cortisol secretion?; (3) Who should have surgical treatment and how should it be performed?; and (4) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected Recommendations: (1) Each adrenal mass requires dedicated adrenal imaging. Recent advances now allow discrimination between risk categories: Homogeneous lesions with Hounsfield unit (HU) ≤ 10 on unenhanced CT are benign and do not require any additional imaging independent of size. All other patients should be discussed in a multidisciplinary expert meeting, but only lesions >4 cm that are inhomogeneous or have HU >20 have sufficiently high risk of malignancy that surgery will be the usual management of choice. (2) Every patient needs a thorough clinical and endocrine work-up to exclude hormone excess including the measurement of plasma or urinary metanephrines and a 1-mg overnight dexamethasone suppression test (applying a cutoff value of serum cortisol ≤50 nmol/L [≤1.8 µg/dL]). Recent studies have provided evidence that most patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post dexamethasone >50 nmol/L (>1.8 µg/dL) harbor increased risk of morbidity and mortality. For this condition, we propose the term "mild autonomous cortisol secretion" (MACS). (3) All patients with MACS should be screened for potential cortisol-related comorbidities that are potentially attributably to cortisol (eg, hypertension and type 2 diabetes mellitus), to ensure these are appropriately treated. (4) In patients with MACS who also have relevant comorbidities surgical treatment should be considered in an individualized approach. (5) The appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health, and patient preference. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. (6) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. Furthermore, we offer recommendations for the follow-up of nonoperated patients, management of patients with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses, and for young and elderly patients with adrenal incidentalomas. Finally, we suggest 10 important research questions for the future.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Diabetes Mellitus Tipo 2 , Anciano , Humanos , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/terapia , Neoplasias de las Glándulas Suprarrenales/patología , Dexametasona , Hidrocortisona
15.
Eur J Endocrinol ; 189(4): S88-S101, 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37801655

RESUMEN

OBJECTIVE: To assess (1) comorbidities associated with and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; > 1.8 µg/dL (>50 nmol/L) cortisol level cut-off following the 1 mg dexamethasone suppression test). DESIGN: Systematic review and meta-analysis. METHODS: Seven databases were searched up to July 14, 2022. Eligible studies were (randomized) trials, cohort studies, and cross-sectional studies assessing comorbidities potentially attributable to cortisol excess or mortality in patients with adrenal incidentaloma with or without MACS or the effects of conservative or surgical management of MACS. Random-effects meta-analysis was performed to estimate pooled proportions (with 95% CIs). RESULTS: In 30 cross-sectional and 16 cohort studies (n = 17 156 patients in total), patients with MACS had a higher prevalence of diabetes (relative risk [RR] 1.44 [1.23-1.69]), hypertension (RR = 1.24 [1.16-1.32]), and dyslipidemia (RR = 1.23 [1.13-1.34]). All-cause mortality (adjusted for confounders) in patients with MACS, assessed in 4 studies (n = 5921), was increased (hazard ratio [HR] = 1.54 [1.27-1.81]). Nine observational studies (n = 856) and 2 randomized trials (n = 107) suggest an improvement in glucometabolic control (RR = 7.99 [2.95-21.90]), hypertension (RR = 8.75 [3.99-19.18]), and dyslipidemia (RR = 3.24 [1.19-8.82]) following adrenalectomy. CONCLUSIONS: The present systematic review and meta-analysis highlight the relevance of MACS, since both cardiometabolic morbidities and mortality appeared to have increased in patients with MACS compared to patients with non-functioning incidentalomas. However, due to heterogeneous definitions, various outcomes, selective reporting, and missing data, the reported pooled estimates need to be interpreted with caution. The small number of patients in randomized trials prevents any strong conclusion on the causality between MACS and these comorbidities.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Dislipidemias , Hipertensión , Humanos , Neoplasias de las Glándulas Suprarrenales/complicaciones , Hidrocortisona , Estudios Transversales , Hipertensión/complicaciones , Dislipidemias/complicaciones
16.
Arch Med Res ; 54(8): 102919, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38040527

RESUMEN

BACKGROUND: Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5-20%) rates highlighted that surgery might be first-line treatment. AIMS: To report on outcomes of ETSS in a cohort of prolactinomas. METHODS: Multicenter retrospective cohort of 137 prolactinoma patients (age 38.2 ± 13.7 years; 61.3% female, median follow-up 28.0 [15.0-55.5] months) operated between 2010-2019 with histopathological confirmation. RESULTS: Median preoperative prolactin levels were 166 (98-837 µg/L; males 996 [159-2145 µg/L] vs. females 129 [84-223 µg/L], p <0.001). 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas were included, whereas no adenoma was detected in 5 (3.6%) patients. Males had larger tumors (macroprolactinomas: 38, 71.7%) vs. 31 (36.9%), p <0.001; giant prolactinomas: 7 (13.2%) vs. 0 (0.0%), (p <0.001). Prolactinomas were graded as KNOSP-3 in 15 (11.5%), and KNOSP-4 in 20 (15.3%) patients. Primary indication was DA intolerance (59, 43.1%); males 14 (26.4%) vs. females 45 (53.6%), p = 0.006. Long-term remission (i.e., DA-free prolactin level <1xULN) was achieved in 87 (63.5%) patients, being higher in intended complete resection (69/92 [75.0%]), and lower in males (25 [47.2%] vs. 62 females [73.8%], p = 0.002). Transient DI (n = 29, 21.2%) was the most frequent complication. CONCLUSIONS: Despite high proportions of macroprolactinoma and KNOSP 3-4, long-term remission rates were 63.5% overall, and 83.3% in microprolactinoma patients. Males had less favorable remission rate compared to females. These findings highlight that ETSS may be a safe and efficacious treatment to manage prolactinoma.


Asunto(s)
Neoplasias Hipofisarias , Prolactinoma , Masculino , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Prolactinoma/cirugía , Prolactinoma/patología , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Estudios Retrospectivos , Prolactina , Agonistas de Dopamina/uso terapéutico , Resultado del Tratamiento
17.
J Clin Endocrinol Metab ; 107(6): 1626-1635, 2022 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-35176767

RESUMEN

CONTEXT: Cold exposure mobilizes lipids to feed thermogenic processes in organs, including brown adipose tissue (BAT). In rodents, BAT metabolic activity exhibits a diurnal rhythm, which is highest at the start of the wakeful period. OBJECTIVE: We investigated whether cold-induced thermogenesis displays diurnal variation in humans and differs between the sexes. METHODS: This randomized crossover study included 24 young and lean male (n = 12) and female (n = 12) participants who underwent 2.5-hour personalized cooling using water-perfused mattresses in the morning (7:45 am) and evening (7:45 pm), with 1 day in between. We measured energy expenditure (EE) and supraclavicular skin temperature in response to cold exposure. RESULTS: In males, cold-induced EE was higher in the morning than in the evening (+54% ±â€…10% vs +30% ±â€…7%; P = 0.05) but did not differ between morning and evening in females (+37% ±â€…9% vs +30% ±â€…10%; P = 0.42). Only in males, supraclavicular skin temperature upon cold increased more in morning than evening (+0.2 ±â€…0.1 °C vs -0.2 ±â€…0.2 °C; P = 0.05). In males, circulating free fatty acid (FFA) levels were increased after morning cold exposure, but not evening (+90% ±â€…18% vs +9% ±â€…8%; P < 0.001). In females, circulating FFA (+94% ±â€…21% vs +20% ±â€…5%; P = 0.006), but also triglycerides (+42% ±â€…5% vs +29% ±â€…4%, P = 0.01) and cholesterol levels (+17% ±â€…2% vs 11% ±â€…2%; P = 0.05) were more increased after cold exposure in morning than in evening. CONCLUSION: Cold-induced thermogenesis is higher in morning than evening in males; however, lipid metabolism is more modulated in the morning than the evening in females.


Asunto(s)
Ritmo Circadiano , Termogénesis , Tejido Adiposo Pardo/metabolismo , Ritmo Circadiano/fisiología , Frío , Estudios Cruzados , Metabolismo Energético , Femenino , Humanos , Masculino , Termogénesis/fisiología
18.
Endocrine ; 75(1): 228-238, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34448099

RESUMEN

PURPOSE: Bone health is compromised in acromegaly resulting in vertebral fractures (VFs), regardless of biochemical remission. Sclerostin is a negative inhibitor of bone formation and is associated with increased fracture risk in the general population. Therefore, we compared sclerostin concentrations between well-controlled acromegaly patients and healthy controls, and assessed its relationship with bone mineral density (BMD), and VFs in acromegaly. METHODS: Seventy-nine patients (mean age 58.9 ± 11.4 years, 49% women) with controlled acromegaly, and 91 healthy controls (mean age 51.1 ± 16.9 years, 59% women) were included. Plasma sclerostin levels (pg/mL) in patients were measured with an ELISA assay, whereas in controls, serum levels were converted to plasma levels by multiplication with 3.6. In patients, VFs were radiographically assessed, and BMD was assessed using dual X-ray absorptiometry. RESULTS: Median sclerostin concentration in controlled acromegaly patients was significantly lower than in healthy controls (104.5 pg/mL (range 45.7-234.7 pg/mL) vs 140.0 pg/mL (range 44.8-401.6 pg/mL), p < 0.001). Plasma sclerostin levels were not related to age, current growth hormone (GH) or insulin-like factor-1 (IGF-1) levels, gonadal state, treatment modality, remission duration, or BMD, VF presence, severity or progression. CONCLUSION: Patients with long-term controlled acromegaly have lower plasma sclerostin levels than healthy controls, as a reflection of decreased osteocyte activity. Further longitudinal studies are needed to establish the course of sclerostin during different phases of disease and its exact effects in acromegalic osteopathy.


Asunto(s)
Acromegalia , Proteínas Adaptadoras Transductoras de Señales/sangre , Fracturas de la Columna Vertebral , Absorciometría de Fotón , Adulto , Anciano , Densidad Ósea , Femenino , Hormona de Crecimiento Humana/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Persona de Mediana Edad , Fracturas de la Columna Vertebral/epidemiología
19.
Psychoneuroendocrinology ; 124: 105081, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33340878

RESUMEN

BACKGROUND: Learned placebo effects induced by pharmacological conditioning affect immune and endocrine outcomes and may offer new possibilities for clinical applications. Whether or not cortisol is subject to this type of associative learning processes, and whether conditioning may affect responses to stress, is currently unclear. METHOD: A randomized placebo-controlled trial was conducted in 48 healthy young women. During acquisition, participants received a pill containing either 100 mg hydrocortisone (unconditioned stimulus) or placebo, paired with a gustatory conditioned stimulus on three consecutive days. During evocation, all participants received placebo paired with the conditioned stimulus, again on three consecutive days. During the third evocation trial, participants underwent a psychosocial stress task. The main outcome parameter salivary cortisol and secondary outcome parameters salivary alpha-amylase, self-reported positive affect and tension, heart rate, and skin conductance level were measured at several time points. RESULTS: Significant baseline group differences on cortisol were found at several time points, which complicate the interpretation of group differences. During the first evocation session, the conditioned group showed a moderately smaller cumulative decrease in salivary cortisol from baseline than the placebo control group. No significant differences were found between the groups on cortisol during the second and third evocation or in response to stress, nor on other outcome measures. CONCLUSION: Although the results provide potential further indications for effects of conditioning on cortisol, baseline differences make it impossible to draw clear conclusions. No indications for possible effects of conditioning on the cortisol stress response or autonomous or affective responses to stress were found.


Asunto(s)
Condicionamiento Clásico , Hidrocortisona , Femenino , Frecuencia Cardíaca , Humanos , Aprendizaje , Efecto Placebo
20.
J Clin Endocrinol Metab ; 106(1): 188-200, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33099640

RESUMEN

CONTEXT: Joint complaints in patients with acromegaly are common, although the long-term disease course is largely unknown. OBJECTIVE: This study aims to evaluate the long-term course of acromegalic arthropathy. DESIGN AND SETTING: A prospective longitudinal cohort study was conducted in controlled acromegaly patients followed at a tertial referral center, with 3 study visits: at baseline and after a median of 2.6 and 9.1 years. PATIENTS: We included 31 patients with biochemically controlled acromegaly for 2 or more years (49% female; median age, 60 years) at baseline. MAIN OUTCOME MEASURES: Radiographic arthropathy of the knee, hip, hand, and cervical and lumbar spine were evaluated using Kellgren and Lawrence (KL) scores, developed for assessment of primary osteoarthritis (OA). Radiographic progression was defined as a KL increase above the smallest detectable change. Joint symptoms were assessed using self-reported questionnaires. Progression was defined using existing clinically important cutoff values. Risk factors for progression were investigated using a multivariable model. RESULTS: All patients had definite radiographic OA at 1 or more joints at baseline. Radiographic progression was observed in 29%, 48%, 84%, and 94% of patients in the knees, hips, hands, and axial joints, respectively. Deterioration in hand-related pain and function was observed in 10 (32.3%) and 11 patients (35.5%), respectively. Solely baseline KL scores of the hip were associated with hip OA progression (OR 1.88; 95% CI, 1.09-3.16). CONCLUSIONS: Acromegalic arthropathy showed significant radiographic progression over 9.1 years of follow-up in patients in remission, whereas clinical progression was observed less frequently. Future studies should focus on adequate prevention and treatment strategies of acromegalic arthropathy.


Asunto(s)
Acromegalia/complicaciones , Acromegalia/terapia , Artropatías , Acromegalia/sangre , Acromegalia/diagnóstico , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Artropatías/diagnóstico , Artropatías/etiología , Artropatías/patología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Países Bajos , Radiografía , Inducción de Remisión
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