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1.
Chemotherapy ; 69(1): 27-34, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37336201

RESUMEN

Trifluridine/tipiracil is approved for the use in later or last-line setting in previously treated metastatic colorectal cancer (mCRC) patients who progressed on standard anti-tumor drugs including 5-fluorouracil (5-FU), irinotecan, oxaliplatin, anti-VEGF and anti-EGFR antibodies, or who are not considered candidates for those standard therapies. In this report, we describe a 67-year-old male patient with KRAS-mutated mCRC and metachronous liver and lung metastasis who failed prior 5-FU- and irinotecan-containing regimens, but then showed long-term disease control for 31 months on single-agent trifluridine/tipiracil given as second-line treatment. According to our experience, trifluridine/tipiracil is a feasible and effective treatment option in earlier but not necessarily last-line therapy in mCRC patients who are not considered candidates for doublet or triplet chemotherapy. Besides its efficacy, it is associated with maintained quality of life and a manageable toxicity profile. Considering increasing age of mCRC patients and their wish for maintaining an independent lifestyle, further research on the use of trifluridine/tipiracil in earlier lines of systemic mCRC therapy is warranted.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Pirrolidinas , Timina , Masculino , Humanos , Anciano , Supervivencia sin Progresión , Uracilo/uso terapéutico , Neoplasias Colorrectales/patología , Trifluridina/uso terapéutico , Trifluridina/efectos adversos , Irinotecán/uso terapéutico , Calidad de Vida , Neoplasias del Colon/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Combinación de Medicamentos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
2.
Front Oncol ; 13: 1237472, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37849815

RESUMEN

Introduction: Differentiated thyroid carcinoma (DTC) in childhood and during adolescence is extremely rare. Pediatric DTC commonly presents with advanced disease at diagnosis including a high prevalence of cervical lymph node metastases and pulmonary metastases. Studies in children with DTC are limited. Therefore, we aimed to evaluate the initial presentation, effectiveness of radioiodine therapy (RIT), and long-term outcome of prepubertal in comparison to pubertal/postpubertal patients. Methods: Eighty-five pediatric and young patients aged 6.4 to 21.9 years with histopathologically confirmed DTC were retrospectively included. They all underwent total thyroidectomy followed by RIT. Initial presentation and outcome of prepubertal and pubertal/postpubertal patients were compared 1 year after RIT, during follow-up, and at the last visit of follow-up. Results: Prepubertal patients presented with significantly higher T and M stages. One year after RIT, 42/81 (52%) patients still presented with evidence of disease (ED). During follow-up of a median of 7.9 years, prepubertal patients were less often in complete remission (58% vs. 82% in pubertal patients). At the last visit of follow-up, 19/80 (24%) patients still had ED without statistical differences between the two groups (42% prepubertal vs. 18% pubertal/postpubertal, p-value 0.06). None of our patients died disease-related over the observed period. Conclusion: Prepubertal children with DTC presented with a more advanced tumor stage at the initial presentation. During follow-up, they present more often with ED. However, at the end of our study, we did not observe statistically relevant differences in patient outcomes between the prepubertal and pubertal/postpubertal groups.

3.
Eur J Endocrinol ; 187(5): 637-650, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-36070424

RESUMEN

Objective: Cortisol measurements are essential for the interpretation of adrenal venous samplings (AVS) in primary aldosteronism (PA). Cortisol cosecretion may influence AVS indices. We aimed to investigate whether cortisol cosecretion affects non-adrenocorticotrophic hormone (ACTH)-stimulated AVS results. Design: Retrospective cohort study at a tertiary referral center. Methods: We analyzed 278 PA patients who underwent non-ACTH-stimulated AVS and had undergone at least a 1-mg dexamethasone suppression test (DST). Subsets underwent additional late-night salivary cortisol (LSC) and/or 24-h urinary free cortisol (UFC) measurements. Patients were studied from 2013 to 2020 with follow-up data of 6 months following adrenalectomy or mineralocorticoid antagonist therapy initiation. We analyzed AVS parameters including adrenal vein aldosterone/cortisol ratios, selectivity, lateralization (LI) and contralateral suppression indices and post-operative ACTH-stimulation. We classified outcomes according to the primary aldosteronism surgical outcome (PASO) criteria. Results: Among the patients, 18.9% had a pathological DST result (1.9-5 µg/dL: n = 44 (15.8%); >5 µg/dL: n = 8 (2.9%)). Comparison of AVS results stratified according to the 1-mg DST (≤1.8 vs >1.8 µg/dL: P = 0.499; ≤1.8 vs 1.8 ≤ 5 vs >5 µg/dL: P = 0.811) showed no difference. Lateralized cases with post DST serum cortisol values > 5 µg/dL had lower LI (≤1.8 µg/dL: 11.11 (5.36; 26.76) vs 1.9-5 µg/dL: 11.76 (4.9; 31.88) vs >5 µg/dL: 2.58 (1.67; 3.3); P = 0.008). PASO outcome was not different according to cortisol cosecretion. Conclusions: Marked cortisol cosecretion has the potential to influence non-ACTH-stimulated AVS results. While this could result in falsely classified lateralized cases as bilateral, further analysis of substitutes for cortisol are required to unmask effects on clinical outcome.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Hiperaldosteronismo , Neoplasias de las Glándulas Suprarrenales/patología , Glándulas Suprarrenales/patología , Hormona Adrenocorticotrópica , Aldosterona , Dexametasona/farmacología , Humanos , Hidrocortisona , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirugía , Antagonistas de Receptores de Mineralocorticoides , Estudios Retrospectivos
4.
J Clin Med ; 11(10)2022 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-35629070

RESUMEN

Primary hyperparathyroidism (pHPT) is a common endocrine disorder due to hyperfunctioning parathyroid glands. To date, the only curing therapy is surgical removal of the dysfunctional gland, making correct detection and localization crucial in order to perform a minimally invasive parathyroidectomy. 18F-Fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) has shown promising results for the detection of pHPT, suggesting superiority over conventional imaging with ultrasounds or scintigraphy. A total of 33 patients with pHPT who had negative or equivocal findings in conventional imaging received 18F-FCH PET/CT preoperatively and were retrospectively included. A pathological hyperfunctional parathyroid gland was diagnosed in 24 cases (positive PET, 72.7%), 4 cases showed equivocal choline uptake (equivocal PET, 12.1%), and in 5 cases, no enhanced choline uptake was evident (negative PET, 15.2%). Twelve of the twenty-four detected adenoma patients underwent surgery, and in all cases, a pathological parathyroid adenoma was resected at the site detected by PET/CT. Two of the six patients without pathological choline uptake who received a parathyroidectomy revealed no evidence of parathyroid adenoma tissue in the histopathological evaluation. This retrospective study analyzes 18F-FCH PET/CT in a challenging patient cohort with pHPT and negative or equivocal conventional imaging results and supports the use of 18F-FCH for the diagnosis of hyperfunctional parathyroid tissue, especially in this patient setting, with a 100% true positive and true negative detection rate. Our study further demonstrates the importance of 18F-FCH PET/CT for successful surgical guidance.

5.
Gland Surg ; 11(4): 651-662, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35531110

RESUMEN

Background: Post thyroidectomy hemorrhage is a potentially life-threatening complication. As the mechanism leading to hypoxemic brain damage and death is still unknown, our aim was to examine the underlaying pathophysiology in an animal model. Methods: A series of experiments was performed in our established model for post thyroidectomy hemorrhage in 6 pigs. First, post thyroidectomy hemorrhage was simulated with an artificial increase of cervical compartment pressure. Second, spontaneous bleeding into the cervical compartment was initiated. Primary outcome measure is the correlation between cerebral oxygenation and cervical compartment pressure. Results: With an increase in cervical compartment pressure apnea could be detected in all experiments. A significant 24.2% (9.5-34.4%) decrease of cerebral oxygenation at time of apnea (47.0%; 38.0-65.0%) compared to baseline values (63.5%; 56.0-74.0%; P=0.043) occurred due increase of cervical compartment pressure concurrent with an impaired cerebral perfusion. Apnea occurred about 200 sec after a 10% decrease of cerebral oxygenation, but 35 sec before a 10% decrease of peripheral oxygenation. Spontaneous bleeding into the cervical compartment causes an increase of cervical compartment pressure reaching levels of the mean arterial blood pressure 56.0 (35.0-72.0) mmHg. Conclusions: Peripheral hypoxemia occurs with relevant delay in time after decrease of cerebral perfusion and cerebral hypoxemia, therefore cerebral hypoxemia seems to be causal for a central apnea. With this evidence of impaired cerebral perfusion and cerebral hypoxemia due to an increased cervical compartment pressure we can disprove the historic theory of tracheal collapse due to a compressive hematoma in post thyroidectomy hemorrhage. A cervical compartment syndrome seems to be causal, not only for brain hypoxemia but also an additional laryngo-pharyngeal mucosal edema.

6.
Endocr Relat Cancer ; 29(6): 285-306, 2022 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-35324454

RESUMEN

Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (n = 10) and kinase signaling-associated cluster 2-related (n = 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib/everolimus, alpelisib/everolimus, alpelisib/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib/everolimus, alpelisib/trametinib) or synergistic effects in cluster 2 (alpelisib/everolimus). Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Antineoplásicos , Paraganglioma , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/tratamiento farmacológico , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Everolimus/uso terapéutico , Humanos , Ratones , Paraganglioma/tratamiento farmacológico , Paraganglioma/genética , Paraganglioma/patología , Feocromocitoma/tratamiento farmacológico , Feocromocitoma/genética , Feocromocitoma/metabolismo , Ácido Zoledrónico/uso terapéutico
8.
Surg Endosc ; 35(12): 6892-6896, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33263179

RESUMEN

BACKGROUND: Body core temperature is an important vital parameter during surgery and anaesthesia. It is influenced by several patient-related and surgery-related factors. Laparoscopy is considered beneficial in terms of a variety of parameters, for example, postoperative pain and length of hospital stay. Non-humidified, non-warmed insufflated CO2 applied during laparoscopy is standard of care. This prospective observational trial therefore evaluates the impact of non-humidified CO2 at room temperature on abdominal temperature and its correlation to body core temperature. METHODS: Seventy patients undergoing laparoscopic surgery were included in this prospective observational study. Temperature was measured oesophageal and abdominal before induction of anaesthesia (T1), right before skin incision (T2), 15 min, 30 min and 60 min after skin incision. All patients were treated according to actual guidelines for perioperative temperature measurement. RESULTS: Body core temperature and abdominal temperature correlated moderately (r = 0.6123; p < 0.0001). Bland-Altman plot for comparison of methods showed an average difference of 0.4 °C (bias - 0.3955; 95% agreement of bias from - 2.365 to 1.574). Abdominal temperature further decreased after establishing pneumoperitoneum (T2: 36.2 °C (35.9/36.4) to T5: 36.1 °C (35.6/36.4); p < 0.0001), whereas oesophageal temperature increased (T2: 36.2 °C (35.9/36.4) to 36.4 °C (36.0/36.7); p = 0.0296). Values of oesophageal and abdominal measurement points differed at T4 (36.3 °C (36.0/36.6) vs. 36.1 °C (35.4/36.6); p < 0.0001) and T5 (36.4 °C (36.0/36.7) vs. 36.1 °C (35.6/36.4) p = 0.0003). CONCLUSION: This prospective observational trial shows the influence of insufflated, non-humidified carbon dioxide at room temperature on abdominal temperature during laparoscopic surgery. We show that carbon dioxide applied at these conditions decreases abdominal temperature and therefore might be a risk factor for perioperative hypothermia.


Asunto(s)
Insuflación , Laparoscopía , Temperatura Corporal , Dióxido de Carbono , Humanos , Humedad , Neumoperitoneo Artificial/efectos adversos , Temperatura
9.
Endocrine ; 70(2): 218-231, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32743767

RESUMEN

PURPOSE: Recurrence after pituitary surgery in Cushing's disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD. METHODS: We systematically screened the literature regarding recurrent and persistent Cushing's disease using the MESH term Cushing's disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review. RESULTS AND CONCLUSIONS: Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrenalectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy). All treatment options have specific advantages, limitations, and side effects. Therefore, treatment decisions have to be individualized according to the specific needs of the patient.


Asunto(s)
Adenoma Hipofisario Secretor de ACTH , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Adenoma Hipofisario Secretor de ACTH/cirugía , Adrenalectomía , Adulto , Niño , Femenino , Humanos , Recurrencia Local de Neoplasia , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/cirugía , Hipófisis/cirugía , Embarazo , Recurrencia , Resultado del Tratamiento
10.
Surg Endosc ; 34(5): 2050-2055, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31342258

RESUMEN

BACKGROUND: Indocyanine green (ICG) fluorescence imaging represents an emerging technology that facilitates the assessment of tissue vascularity, tissue distinction, and tumor localization during surgery. The aim of this study was to investigate the potential role of ICG imaging during laparoscopic partial adrenalectomy. METHODS: Indocyanine fluorescence imaging was carried out during laparoscopic partial adrenalectomy for bilateral pheochromocytoma and bilateral Cushing's syndrome. A first bolus of 5 mg ICG was applied intravenously upon exposure of the retroperitoneal plane to identify the adrenal borders. The fluorescence was visualized using a Storz® NIR/ICG endoscopic system. As the camera of this system detects NIR light as a blue signal, the well-vascularized adrenal tissue was expected to show a strong fluorescence in the blue color channel in contrast to the surrounding adipose tissue. Following partial adrenalectomy, a second bolus of 5 mg ICG was applied intravenously to evaluate the vascularity of the remaining adrenal tissue. RESULTS: We investigated six adrenal glands from three patients undergoing bilateral partial adrenalectomy. The indication for surgery was pheochromocytoma in two patients and Cushing's syndrome with bilateral adenomas in one patient. Regarding left adrenalectomies, ICG imaging was helpful in visualizing the adrenal borders and the adrenal vein. Further, it facilitated the identification of the hypofluorescent pheochromocytoma and to resect the entire tumor. On the right side, due to the more apparent anatomy, ICG imaging did not contribute to the conduct of the operation. Four adrenal remnants showed a strong vascularization and two remnants were only reasonably vascularized. CONCLUSION: ICG fluorescence may be helpful in guiding partial adrenalectomy and assessing the vascularity of remaining adrenal tissue.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Verde de Indocianina/uso terapéutico , Imagen Óptica/métodos , Neoplasias de las Glándulas Suprarrenales/patología , Animales , Femenino , Humanos , Masculino , Estudios Prospectivos
11.
Exp Clin Endocrinol Diabetes ; 128(4): 246-254, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31698477

RESUMEN

CONTEXT: Recent studies support a bidirectional interaction between aldosterone and parathyroid hormone (PTH), possibly increasing the individual cardiovascular risk. Primary aldosteronism (PA) and primary hyperparathyroidism can occur simultaneously. OBJECTIVE: Our aim was to investigate the prevalence of hyperparathyroidism in PA. PATIENTS: We performed a case finding of primary hyperparathyroidism in a retrospective series of 503 patients with PA (cohort 1). We analysed primary and secondary hyperparathyroidism in 141 prospective PA patients who underwent PTH, serum calcium and phosphate measurements at time of diagnosis of PA (cohort 2). RESULTS: The prevalence for primary hyperparathyroidism was 1.2% in cohort 1, and 2.1% in cohort 2. Secondary hyperparathyroidism was found in 54.6% of the patients. Patients with secondary hyperparathyroidism had significantly higher aldosterone and lower potassium levels and took more antihypertensive medications compared to those with normal PTH levels. In multivariate analysis, aldosterone and 25-hydroxyvitamin D levels were significantly correlated with serum PTH levels. There was a nonsignificant trend to a higher cardiovascular morbidity in patients with secondary hyperparathyroidism. Patients with aldosterone producing adenoma had significantly higher PTH levels compared to patients with bilateral adrenal hyperplasia. After treatment, there was a significant decrease of PTH levels in both groups. CONCLUSION: Patients with PA frequently have primary or secondary hyperparathyroidism, which is alleviated by correction of PA by surgical or medical means. Patients affected by secondary hyperparathyroidism seem to have a more severe phenotype of PA and have a trend towards more cardiovascular co-morbidities.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Hiperaldosteronismo/epidemiología , Hiperparatiroidismo Secundario/epidemiología , Sistema de Registros , Adulto , Enfermedades Cardiovasculares/sangre , Comorbilidad , Femenino , Alemania/epidemiología , Humanos , Hidroxicolecalciferoles/sangre , Hiperaldosteronismo/sangre , Hiperparatiroidismo Secundario/sangre , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Fenotipo , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
12.
Int J Endocrinol ; 2019: 4687951, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31662746

RESUMEN

OBJECTIVE: To investigate the feasibility of near-infrared autofluorescence (AF) and indocyanine green (ICG) fluorescence to identify parathyroid glands intraoperatively. METHODS: Fluorescence imaging was carried out during open parathyroid and thyroid surgery. After visual identification, parathyroid glands were exposed to near-infrared (NIR) light with a wavelength between 690 and 770 nm. The camera of the Storz® NIR/ICG endoscopic system used detects NIR light as a blue signal. Therefore, parathyroid AF was expected to be displayed in the blue color channel in contrast to the surrounding tissue. Following AF imaging, a bolus of 5 mg ICG was applied intravenously. ICG fluorescence was detected using the same NIR/ICG imaging system. Well-vascularized parathyroid glands were expected to show a strong fluorescence in contrast to surrounding lymphatic and adipose tissue. RESULTS: We investigated 78 parathyroid glands from 50 patients. 64 parathyroid glands (82%) displayed AF showing the typical bluish violet color. 63 parathyroid glands (81%) showed a strong and persistent fluorescence after application of ICG. The sensitivity of identifying a parathyroid gland by AF was 82% (64 true positive and 14 false negative results), while ICG imaging showed a sensitivity of 81% (63 true positive and 15 false negative results). The Fisher exact test revealed no significant difference between both groups at p < 0.05. Neither lymph nodes nor adipose tissue revealed substantial AF or ICG fluorescence. CONCLUSION: AF and ICG fluorescence reveal a high degree of sensitivity in identifying parathyroid glands. Further, ICG imaging facilitates the assessment of parathyroid perfusion. However, in the current setting both techniques are not suitable as screening tools to identify parathyroid glands at an early stage of the operation.

13.
Molecules ; 24(14)2019 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-31337096

RESUMEN

Injury to parathyroid glands during thyroid and parathyroid surgery is common and postoperative hypoparathyroidism represents a serious complication. Parathyroid glands possess a unique autofluorescence in the near-infrared spectrum which could be used for their identification and protection at an early stage of the operation. In the present study parathyroid autofluorescence was visualized intraoperatively using a standard Storz laparoscopic near-infrared/indocyanine green (NIR/ICG) imaging system with minor modifications to the xenon light source (filtered to emit 690 nm to 790 nm light, less than 1% in the red and green above 470 nm and no blue light). During exposure to NIR light parathyroid tissue was expected to show autofluorescence at 820 nm, captured in the blue channel of the camera. Over a period of 5 years, we investigated 205 parathyroid glands from 117 patients. 179 (87.3%) glands were correctly identified by their autofluorescence. Surrounding structures such as thyroid, lymph nodes, muscle, or adipose tissue did not reveal substantial autofluorescence. We conclude that parathyroid glands can be identified by their unique autofluorescence at an early stage of the operation. This may help to preserve these fragile structures and their vascularization and lower the rate of postoperative hypocalcemia.


Asunto(s)
Imagen Óptica , Glándulas Paratiroides/diagnóstico por imagen , Humanos , Cuidados Intraoperatorios , Glándulas Paratiroides/cirugía , Paratiroidectomía , Espectroscopía Infrarroja Corta , Glándula Tiroides/cirugía , Tiroidectomía
14.
J Clin Endocrinol Metab ; 104(11): 5658-5664, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31225874

RESUMEN

CONTEXT: Primary aldosteronism (PA) represents a secondary form of arterial hypertension that can be cured by surgery. Evidence of adrenal insufficiency (AI) was recently found in patients with PA who had undergone unilateral adrenalectomy (uADX). OBJECTIVE: To study the incidence and long-term outcome of postoperative AI after uADX for PA. DESIGN: Prospective registry study (August 2014 until the end of 2018). SETTING: Tertiary referral center. PATIENTS: One hundred consecutive patients undergoing uADX for PA were included. All patients underwent postoperative ACTH stimulation testing. INTERVENTION: Postoperative ACTH stimulation testing to identify patients with AI. MAIN OUTCOME MEASURES: Incidence of patients with postoperative AI and definition of long-term outcome. RESULTS: Twenty-seven percent of patients developed postoperative AI. Of these, 48% had postoperative ACTH stimulation serum cortisol levels ≤13.5 µg/dL (severe AI); 52% were classified into the group with moderate AI (stimulated serum cortisol levels: 13.5 to 17 µg/dL). Patients with severe AI required significantly longer hydrocortisone replacement therapy than the moderate group (median [25th, 75th percentiles]: 353 [294, 476] days; 95% CI: 284 to 322 days; vs 74 [32, 293] days; 95% CI: 11 to 137 days; P = 0.016). One patient with severe AI was hospitalized for an acute adrenal crisis. With a cumulative follow-up of 14.5 years, this produced an incidence rate of 6.9 adrenal crises per 100 patient-years. CONCLUSION: We suggest performing postoperative ACTH stimulation tests in all patients who undergo uADX for PA.


Asunto(s)
Insuficiencia Suprarrenal/epidemiología , Adrenalectomía/efectos adversos , Hidrocortisona/sangre , Hiperaldosteronismo/cirugía , Insuficiencia Suprarrenal/sangre , Insuficiencia Suprarrenal/etiología , Hormona Adrenocorticotrópica/sangre , Adulto , Femenino , Humanos , Hiperaldosteronismo/sangre , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Sistema de Registros , Resultado del Tratamiento
16.
J Clin Endocrinol Metab ; 103(12): 4543-4552, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-30113683

RESUMEN

Context: Primary aldosteronism (PA) represents the most frequent form of endocrine hypertension. Hyperaldosteronism and hypercortisolism both induce excessive left ventricular hypertrophy (LVH) compared with matched essential hypertensives. In recent studies frequent cosecretion of cortisol and aldosterone has been reported in patients with PA. Objective: Our aim was to investigate the impact of cortisol cosecretion on LVH in patients with PA. We determined 24-hour excretion of mineralocorticoids and glucocorticoids by gas chromatography-mass spectrometry and assessed cardiac remodeling using echocardiography initially and 1 year after initiation of treatment of PA. Patients: We included 73 patients from the Munich center of the German Conn's registry: 45 with unilateral aldosterone-producing adenoma and 28 with bilateral adrenal hyperplasia. Results: At the time of diagnosis, 85% of patients with PA showed LVH according to left ventricular mass index [(LVMI); median 62.4 g/m2.7]. LVMI correlated positively with total glucocorticoid excretion (r2 = 0.076, P = 0.018) as well as with tetrahydroaldosterone excretion (r2 = 0.070, P = 0.024). Adrenalectomy led to significantly reduced LVMI in aldosterone-producing adenoma (P < 0.001) whereas mineralocorticoid receptor antagonist therapy in bilateral adrenal patients with hyperplasia reduced LVMI to a lesser degree (P = 0.024). In multivariate analysis, the decrease in LVMI was positively correlated with total glucocorticoid excretion and systolic 24-hour blood pressure, but not with tetrahydroaldosterone excretion. Conclusion: Cortisol excess appears to have an additional impact on cardiac remodeling in patients with PA. Treatment of PA by either adrenalectomy or mineralocorticoid receptor antagonist improves LVMI. This effect was most pronounced in patients with high total glucocorticoid excretion.


Asunto(s)
Neoplasias de la Corteza Suprarrenal/complicaciones , Adenoma Corticosuprarrenal/complicaciones , Hidrocortisona/sangre , Hiperaldosteronismo/complicaciones , Hipertrofia Ventricular Izquierda/etiología , Corteza Suprarrenal/metabolismo , Corteza Suprarrenal/cirugía , Neoplasias de la Corteza Suprarrenal/sangre , Neoplasias de la Corteza Suprarrenal/terapia , Adrenalectomía , Adenoma Corticosuprarrenal/sangre , Adenoma Corticosuprarrenal/terapia , Adulto , Aldosterona/sangre , Aldosterona/metabolismo , Ecocardiografía , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Hidrocortisona/metabolismo , Hiperaldosteronismo/sangre , Hiperaldosteronismo/terapia , Hipertrofia Ventricular Izquierda/sangre , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/epidemiología , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Prevalencia
18.
Eur J Clin Invest ; 47(5): 372-377, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28299775

RESUMEN

INTRODUCTION: The correct differentiation between unilateral and bilateral adrenal involvement in patients with primary aldosteronism (PA) is of utmost importance to justify surgical treatment. The aim of this study was to determine the accuracy of adrenal imaging compared to adrenal venous sampling (AVS), histopathology and postoperative outcome. METHODS: The data of all patients with unequivocal AVS who underwent unilateral laparoscopic adrenalectomy for primary aldosteronism between May 2004 and April 2015 were entered in this retrospective study. We compared computed tomography (CT) and magnetic resonance imaging (MRI) results with corresponding AVS data, histopathology findings and postoperative outcome. RESULTS: A total of 175 patients underwent unilateral laparoscopic adrenalectomy for primary aldosteronism. AVS was successful in 152 patients and postoperative outcome available in 148 patients. Despite unilateral disease according to AVS results, bilateral normal glands were seen in 15 MRI (17·2%) and 7 CT scans (8·5%), respectively. Unilateral enlargement of the nonhypersecreting adrenal gland was found in three MRI (3·5%) and 10 CT scans (12·2%) of patients who showed aldosterone hypersecretion deriving from the contralateral gland. Fifteen MRI (17·2%) and 18 CT scans (22·0%) revealed bilateral adrenal pathology despite unilateral aldosterone hypersecretion. CONCLUSION: The accuracy of CT and magnetic resonance imaging in predicting unilateral disease is poor. AVS appears to be an essential diagnostic step to identify those patients who may benefit from unilateral adrenalectomy.


Asunto(s)
Neoplasias de la Corteza Suprarrenal/diagnóstico por imagen , Adenoma Corticosuprarrenal/diagnóstico por imagen , Hiperaldosteronismo/diagnóstico por imagen , Neoplasias de la Corteza Suprarrenal/diagnóstico , Neoplasias de la Corteza Suprarrenal/cirugía , Enfermedades de las Glándulas Suprarrenales/diagnóstico , Enfermedades de las Glándulas Suprarrenales/diagnóstico por imagen , Enfermedades de las Glándulas Suprarrenales/patología , Enfermedades de las Glándulas Suprarrenales/cirugía , Adrenalectomía , Adenoma Corticosuprarrenal/diagnóstico , Adenoma Corticosuprarrenal/cirugía , Adulto , Anciano , Aldosterona/análisis , Recolección de Muestras de Sangre , Femenino , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirugía , Hiperplasia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Venas , Adulto Joven
19.
Horm Metab Res ; 49(3): 208-213, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28222463

RESUMEN

Catecholamine excess from pheochromocytoma results in cardiovascular symptoms such as arterial hypertension and tachycardia and induces metabolic alterations including glucose intolerance and increase in resting metabolic rate. The objective of our study was to investigate the effect of surgical cure of pheochromocytoma on body-mass-index and the correlation of body-mass-index changes to preoperative endocrine parameters. Pheochromocytoma patients from the Munich ENSAT Registry were matched (1:2) for age and gender to patients from the German Conn's Registry, who had undergone surgery for aldosterone-producing-adenomas. Thereby, 43 pheochromocytoma patients (17 males/26 females) and 86 aldosterone-producing-adenoma patients were analyzed for body-mass-index, blood pressure, and catecholamine levels before and one year after adrenalectomy. Seventy-four percent of pheochromocytoma patients were hypertensive preoperatively and 48% one year postoperatively. Systolic blood pressure did not differ significantly in pre- and postoperative measurements whereas diastolic blood pressure was significantly reduced over time. Moreover, pheochromocytoma patients gained body weight (p<0.001) one year following adrenalectomy accompanied by significant increases in body-mass-index, whereas aldosterone-producing adenoma patients displayed a slight weight loss. Despite weight gain, diagnosis of diabetes mellitus dropped from 9 of 43 investigated pheochromocytoma patients at baseline to 4 at follow-up. A significant correlation between body-mass-index changes to the preoperative catecholamine levels was found only for urinary normetanephrines. These data suggest that normalization of chronic catecholamine excess by adrenalectomy is associated with an increase in body-mass-index, which is more pronounced in patients with high preoperative levels of urinary normetanephrines.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Adrenalectomía , Índice de Masa Corporal , Feocromocitoma , Sistema de Registros , Neoplasias de las Glándulas Suprarrenales/sangre , Neoplasias de las Glándulas Suprarrenales/fisiopatología , Neoplasias de las Glándulas Suprarrenales/cirugía , Neoplasias de las Glándulas Suprarrenales/orina , Adulto , Anciano , Presión Sanguínea , Catecolaminas/sangre , Catecolaminas/orina , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Feocromocitoma/sangre , Feocromocitoma/fisiopatología , Feocromocitoma/cirugía , Feocromocitoma/orina , Estudios Retrospectivos
20.
J Biomed Opt ; 22(1): 16013, 2017 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-28118427

RESUMEN

Optical coherence tomography (OCT) is a noninvasive high-resolution imaging technique that permits the detection of cancerous and precancerous lesions of the uterine cervix. The purpose of this study was to evaluate a new system that integrates an OCT device into a microscope. OCT images were taken from loop electrosurgical excision procedure (LEEP) specimens under microscopic guidance. The images were blinded with respect to their origin within the microscopic image and analyzed independently by two investigators using initially defined criteria and later compared to the corresponding histology. Sensitivity and specificity were calculated with respect to the correct identification of high-grade squamous intraepithelial lesions (HSIL). The interinvestigator agreement was assessed by using Cohen's kappa statistics. About 160 OCT images were obtained from 20 LEEP specimens. Sixty randomly chosen images were used to define reproducible criteria for evaluation. The assessment of the remaining 100 images showed a sensitivity of 88% (second investigator 84%) and a specificity of 69% (65%) in detecting HSIL. Surgical microscopy-guided OCT appears to be a promising technique for immediate assessment of microanatomical changes. In the gynecological setting, the combination of OCT with a colposcope may improve the detection of high-grade squamous intraepithelial lesions.


Asunto(s)
Microscopía/métodos , Tomografía de Coherencia Óptica/métodos , Displasia del Cuello del Útero/diagnóstico por imagen , Neoplasias del Cuello Uterino/diagnóstico por imagen , Femenino , Humanos , Sensibilidad y Especificidad
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