RESUMEN

Introduction: Patients with primary adrenal insufficiency (PAI) suffer from increased risk of infection, adrenal crises and have a higher mortality rate. Such dismal outcomes have been inferred to immune cell dysregulation because of unphysiological cortisol replacement. As the immune landscape of patients with different types of PAI has not been systematically explored, we set out to immunophenotype PAI patients with different causes of glucocorticoid (GC) deficiency. Methods: This cross-sectional single center study includes 28 patients with congenital adrenal hyperplasia (CAH), 27 after bilateral adrenalectomy due to Cushing's syndrome (BADx), 21 with Addison's disease (AD) and 52 healthy controls. All patients with PAI were on a stable GC replacement regimen with a median dose of 25 mg hydrocortisone per day. Peripheral blood mononuclear cells were isolated from heparinized blood samples. Immune cell subsets were analyzed using multicolor flow cytometry after four-hour stimulation with phorbol myristate acetate and ionomycin. Natural killer (NK-) cell cytotoxicity and clock gene expression were investigated. Results: The percentage of T helper cell subsets was downregulated in AD patients (Th1 p = 0.0024, Th2 p = 0.0157, Th17 p < 0.0001) compared to controls. Cytotoxic T cell subsets were reduced in AD (Tc1 p = 0.0075, Tc2 p = 0.0154) and CAH patients (Tc1 p = 0.0055, Tc2 p = 0.0012) compared to controls. NKCC was reduced in all subsets of PAI patients, with smallest changes in CAH. Degranulation marker CD107a expression was upregulated in BADx and AD, not in CAH patients compared to controls (BADx p < 0.0001; AD p = 0.0002). In contrast to NK cell activating receptors, NK cell inhibiting receptor CD94 was upregulated in BADx and AD, but not in CAH patients (p < 0.0001). Although modulation in clock gene expression could be confirmed in our patient subgroups, major interindividual-intergroup dissimilarities were not detected. Discussion: In patients with different etiologies of PAI, distinct differences in T and NK cell-phenotypes became apparent despite the use of same GC preparation and dose. Our results highlight unsuspected differences in immune cell composition and function in PAI patients of different causes and suggest disease-specific alterations that might necessitate disease-specific treatment.

Asunto(s)

RESUMEN

Severe uncontrolled Cushing's syndrome (CS) is an acute life-threatening condition. As it is often not responsive to medical therapy, emergency bilateral adrenalectomy (BA) may present the only therapeutic option. Moreover, multiple bone fractures, representing one of the clinical consequences of hypercortisolism, may not permit both prone and lateral patient's positioning during surgery, thus making minimally invasive approaches nonfeasible. We report our preliminary experience with an alternative approach in this selected patients' category. Among 613 patients who underwent endoscopic adrenalectomy at our centre (34-5.6% BA) between January 1997 and October 2021, 3 patients were scheduled for laparoscopic transabdominal anterior bilateral adrenalectomy (La-TABA). Surgery was performed with patient in supine position, with fastened arms and legs to allow Trendelenburg and anti-Trendelenburg movements and lateral rotations. The procedure consisted in a synchronous bilateral adrenalectomy. A modern multi-articulated operative table provided rotations on the right and left side to perform left and right adrenalectomy, respectively. One male and two female patients with a mean age of 34 ± 3.1 years underwent La-TABA. Mean operative time was 200 ± 138.3 min. No perioperative complications were registered. Mean postoperative hospital stay was 8 ± 4.4 days. In very severe ACTH-dependent CS, BA should be performed as soon as possible. La-TABA may represent the most appropriate therapeutic option, as this patients' category is not able to tolerate prone and lateral positioning required during the conventional surgery. Despite the higher technical complexity of the procedure compared with the other endoscopic approaches to adrenalectomy, it retains the benefits of minimally invasive surgery in terms of postoperative complications and recovery.

Asunto(s)

RESUMEN

Neonatal cushing syndrome (NCS) is a rare disease that results from prolonged exposure to high cortisol levels. McCune-Albright syndrome (MAS) is an exceedingly rare genetic disorder characterized by cafe-au-lait skin spots, bone fibrous dysplasia and multiple endocrinopathies. We describe a case of a premature neonate with Intrauterine Growth Retardation who presented with hypercortisolemia, neonatal transaminitis and cardiac dysfunction. Further evaluation revealed significant bilateral adrenal hyperplasia leading to the diagnosis of NCS as part of MAS. Despite maximum medical therapy, including metyrapone, the baby's refractory hypertension, hyperglycemia and persistent failure to thrive (weight of 1.4 kg at corrected age 38 weeks) necessitated bilateral adrenalectomy. This case did not initially demonstrate the classic MAS triad, notably, the absence of skeletal manifestations. There has been no previous description of a baby who has had all the early life-threatening features present and survived beyond 18 months. This case highlights the severity of the phenotype and the challenges involved in diagnosing and treating NCS and MAS in neonates.

RESUMEN

CONTEXT: Cortisol-lowering drugs may not restore a normal cortisol secretion in Cushing disease (CD). OBJECTIVE: This work aimed to assess the long-term cortisol exposure in medically treated CD patients using hair-cortisol (HF) and hair-cortisone (HE) measurement. METHODS: This multicenter prospective study included 3 groups of female patients: CushMed = 16 treated with a stable cortisol-lowering drug dosage and normal urinary free cortisol (UFC); CushSurg = 13 cured by pituitary surgery; CushBla = 15 receiving stable recommended doses of hydrocortisone following bilateral adrenalectomy. Patients were evaluated for 3 months with their usual treatments. Two late-night saliva and 24-hour urine samples were collected monthly in CushMed, and at study end in CushSurg and CushBla patients. A 3-cm hair sample was collected at study end from all patients. Main outcome measures included clinical score and centralized measurement of UFC, late-night salivary cortisol (LNSF), late-night salivary cortisone (LNSE), HE, HF. RESULTS: Despite having almost all UFCs normalized, CushMed patients exhibited increased HE as compared to CushSurg controls (P = .003). CushMed patients also had increased clinical score (P = .001), UFC (P = .03), LNSF, LNSE (P = .0001), and variability in the latter parameters (P = .004). CushBla patients had increased HF and HE, contrasting with LNSEs similar to CushSurg patients. Six of 15 CushMed patients exhibited increased HE concentrations and had increased antihypertensive drug dosage compared to CushMed patients with normal HE (P = .05). CONCLUSION: Despite normalized UFCs, a subset of medically treated CD patients displays an altered circadian rhythm of serum cortisol. A single HE measurement identifies chronic mild persistent hypercortisolism and could replace multiple saliva analyzes to monitor medical treatments in CD patients once UFC is normalized.

Asunto(s)

RESUMEN

Nelson syndrome is a rare and potentially life-threatening complication of treatment with total bilateral adrenalectomy for women with Cushing disease. A successful term pregnancy following fertility treatment in a patient with Nelson syndrome is presented. Our study provides guidance in the prenatal and intrapartum management of this condition. A case report and a systematic review of 14 papers describing 50 pregnancies are presented. An electronic database search included Medline (1946 to September 2022), Embase (1980 to September 2022), Cochrane Library, and UKOSS. A small number of pregnancies in women with Nelson syndrome are reported in literature, but there are no guidelines. Some authors detail the prenatal care provided to their patients. Four studies report prenatal monitoring with visual field checks and two report monitoring with X-rays. Five studies report the use of parenteral hydrocortisone at the time of delivery. Where described, women delivered appropriately grown newborns at term, with timing and mode of delivery dictated by obstetric indications. Preconception counseling and optimization of maternal health status improve pregnancy outcomes in women with Nelson syndrome. Multidisciplinary review in a combined obstetric-endocrine prenatal clinic is ideal. Awareness about potential complications during pregnancy and the postnatal period is crucial in providing optimal care to the mother and baby.

Asunto(s)

RESUMEN

PURPOSE: We aimed to evaluate and compare the clinical, biochemical and radiological profile and outcomes of patients with ectopic ACTH syndrome (EAS) and Cushing disease (CD) treated over a period of 10 years (2013-2022). METHODS: In this ambispective observational study, we collected data for 146 patients with ACTH-dependent CS (EAS, n = 23; CD, n = 94; occult ACTH source, n = 29). Relevant details were filled in a predesigned proforma and outcomes were ascertained at the most recent visit. RESULTS: EAS was more common in males (65.2 vs. 27.6%, p < 0.001). Patients with EAS had a shorter duration of symptoms [12 (6-12) vs. 31.5 (15-48) months, p < 0.001] and were more likely to have hypokalemia (82.6 vs. 21.0%, p = 0.001), pedal edema (65.2 vs. 34.2%, p = 0.015), weight loss (34.8 vs. 4.0%, p < 0.001) and systemic infection (30.4 vs. 6.5%, p = 0.006). They also had significantly higher 8 a.m. serum cortisol, midnight serum and salivary cortisol and 8 a.m. plasma ACTH levels. Bronchial carcinoid (n = 10, 43.5%) was the most common etiology of EAS. Bilateral adrenalectomy was performed in 11 (47.8%) patients with EAS. Eight patients (34.8%) with EAS died at the last follow-up, of whom 7 (87.5%) had metastatic disease. In CD group, overall remission rate was 69.4% (56.1%, early and 13.3%, delayed) and 26.3% of patients with an initial remission had recurrence. CONCLUSIONS: Bronchial carcinoid was the most common cause of EAS in our cohort. Bilateral adrenalectomy was performed in approximately every 1 in 2 patients with EAS and approximately every 1 in 3 patients expired till the last follow-up.

Asunto(s)

RESUMEN

Nelson's syndrome is a potentially severe condition that may develop in patients with Cushing's disease treated with bilateral adrenalectomy. Its management can be challenging. Pituitary surgery followed or not by radiotherapy offers the most optimal tumour control, whilst pituitary irradiation alone needs to be considered in cases requiring intervention and are poor surgical candidates. Observation is an option for patients with small lesions, not causing mass effects to vital adjacent structures but close follow-up is required for a timely detection of corticotroph tumour progression and for further treatment if required. To date, no medical therapy has been consistently proven to be effective in Nelson's syndrome. Pharmacotherapy, however, should be considered when other management approaches have failed. A subset of patients with Nelson's syndrome may develop further tumour growth after primary treatment, and, in some cases, a truly aggressive tumour behaviour can be demonstrated. In the absence of evidence-based guidance, the management of these cases is individualized and tailored to previously offered treatments. Temozolomide has been used in patients with aggressive Nelson's with no consistent results. Development of tumour-targeted therapeutic agents are an unmet need for the management of aggressive cases of Nelson's syndrome.

Asunto(s)

RESUMEN

Corticotroph tumor progression after bilateral adrenalectomy/Nelson's syndrome (CTP-BADX/NS) is a severe complication of bilateral adrenalectomy (BADX). The aim of our study was to investigate the prevalence, presentation and outcome of CTP-BADX/NS in patients with Cushing's disease (CD) included in the European Registry on Cushing's Syndrome (ERCUSYN). We examined data on 1045 CD patients and identified 85 (8%) who underwent BADX. Of these, 73 (86%) had follow-up data available. The median duration of follow-up since BADX to the last visit/death was 7 years (IQR 2-9 years). Thirty-three patients (45%) experienced CTP-BADX/NS after 3 years (1.5-6) since BADX. Cumulative progression-free survival was 73% at 3 years, 66% at 5 years and 46% at 10 years. CTP-BADX/NS patients more frequently had a visible tumor at diagnosis of CD than patients without CTP-BADX/NS (P < 0.05). Twenty-seven CTP-BADX/NS patients underwent surgery, 48% radiotherapy and 27% received medical therapy. The median time since diagnosis of CTP-BADX/NS to the last follow-up visit was 2 years (IQR, 1-5). Control of tumor progression was not achieved in 16 of 33 (48%) patients, of whom 8 (50%) died after a mean of 4 years. Maximum adenoma size at diagnosis of CD was associated with further tumor growth in CTP-BADX/NS despite treatment (P = 0.033). Diagnosis of CTP-BADX/NS, older age, greater UFC levels at diagnosis of CD and initial treatment predicted mortality. In conclusion, CTP-BADX/NS was reported in 45% of the ERCUSYN patients who underwent BADX, and control of tumor growth was reached in half of them. Future studies are needed to establish effective strategies for prevention and treatment.

Asunto(s)

RESUMEN

Resumen: Presentamos un caso de una paciente femenina de 27 años, con síndrome de Cushing ACTH dependiente con hipercortisolismo severo, causado por un macroadenoma hipofisario recurrente y resistente pese a dos cirugías transesfenoidales, radioterapia y terapia médica. Dada la falla en las diferentes terapias se realiza una adrenalectomía bilateral como tratamiento definitivo. La paciente fallece en el posoperatorio por causa no clara. Si bien la adrenalectomía bilateral ha sido reportada como un tratamiento efectivo en pacientes con enfermedad de Cushing, se ha relacionado con una mortalidad significativa vinculada con la severidad del hipercortisolismo y las comorbilidades presentes. En este caso la adrenalectomía izquierda se tuvo que convertir a cielo abierto, asociada con mayor morbimortalidad.

Abstract: The study presents the case of a 27-year-old female patient with adrenocorticotropic hormone (ACTH) dependent Cushing's disease and severe hypercortisolism caused by recurrent pituitary macroadenoma that was resistant to treatment despite two transsphenoidal surgeries, radiotherapy and medical treatment. Upon failure of the different therapies a bilateral adrenalectomy was performed as the final treatment. The patient died in after surgery although the case of death was not clear. Despite bilateral adrenalectomy having been reports as an effective treatment in patients with Cushing's disease, it has been related to significant mortality rates in connection with the severity of hypercortisolism and existing comorbilities. In this case the left adrenalectomy ended up being an open surgery, which is associated to a higher mortality rate.

Resumo: Apresentamos o caso de uma paciente de 27 anos com síndrome de Cushing ACTH-dependente com hipercortisolismo grave causado por macroadenoma hipofisário, recorrente e resistente, apesar de haver sido submetida a duas cirurgias transesfenoidal, radioterapia e terapia medicamentosa. Diante do fracasso das diferentes terapias, foi realizada adrenalectomia bilateral como tratamento definitivo. A paciente faleceu no pós-operatório por causa não esclarecida. Embora a adrenalectomia bilateral tenha sido relatada como tratamento eficaz em pacientes com doença de Cushing, ela tem sido associada a mortalidade significativa relacionada à gravidade do hipercortisolismo e às comorbidades presentes. Neste caso, a adrenalectomia esquerda teve que ser convertida para cirurgia aberta, associada a maior morbimortalidade.

Asunto(s)

RESUMEN

INTRODUCTION: Laparoscopic bilateral adrenalectomy (BAD) is one of the treatments of Cushing's Disease (CD), but its indications and outcome is debated. METHODS: The literature on BAD was reviewed as part of a work performed for the Cushing's disease guideline. RESULTS: The surgical morbidity of BAD is reported between 10 and 18% and no mortality has been reported in the largest series. Because of the endocrine sacrifice it will be mostly performed after a multidisciplinary team discussion in selected cases of refractory CD (mostly after failure of pituitary surgery and/or medical treatment). It is also frequently discussed in female patients desiring pregnancy. Corticotroph tumor progression occurs in 40% of the patients but is in most patients manageable when detected early by a careful long term monitoring with pituitary MRI and ACTH assays after BAD. CONCLUSION: BAD is a safe and effective treatment of CD used in specific situations and requiring long term monitoring.

Asunto(s)

RESUMEN

Primary aldosteronism (PA) is a frequent cause of secondary hypertension. The main cause of PA is bilateral adrenal hyperplasia, and treatment is usually medical with mineralocorticoid receptor antagonists (MRAs) such as spironolactone or eplerenone. In this paper, we present a rare clinical case of a middle-aged female with refractory arterial hypertension and hypokalemia that complementary medical tests confirmed PA due to bilateral hyperplasia, and despite a maximum dose of spironolactone and oral potassium supplements, there was no clinical response. Because of this, finally, the patient needed surgical treatment based on bilateral adrenalectomy, which was effective. This is unusual and poorly described in the medical literature.

RESUMEN

Objetivo: Describir las característicasclínicas y los resultados perioperatorios de la adrenalectomía bilateral laparoscópica (ABL) en 5 pacientestratados con diagnóstico de Síndrome de Cushing Ectópico (SCE).Material y método: Se realizó un estudio retrospectivo y descriptivo de todos los pacientes con SCEsometidos a una ABL, entre enero de 2009 y junio de2017. Todos los pacientes fueron evaluados por unequipo multidisciplinario que decidió conjuntamente elmomento más adecuado para la cirugía. Fueron analizados los siguientes datos protocolares: edad, sexo, origen del tumor secretor, duración del hipercortisolismo,motivo de internación, manejo terapéutico inicial, datosbioquímicos (cortisol sérico preoperatorio, ACTH plasmática y cortisol libre urinario), datos quirúrgicos (vía deabordaje, tiempo quirúrgico, tipo de cirugía, necesidadde conversión a cirugía abierta), datos perioperatorios (tiempo de internación postoperatoria, complicacionessegún la escala de Clavien-Dindo, mortalidad, tasa decuración clínica y tasa de curación bioquímica, tiempode seguimiento).Resultados: Cinco pacientes fueron sometidos a ABL.El abordaje fue mínimamente invasivo, ya sea transperitoneal (n=3) o retroperitoneoscópico posterior (n=2). Eltiempo de internación fue de 23,4 días (r=4-81). Ningún paciente falleció por complicaciones quirúrgicas, ytodos lograron la curación bioquímica y clínica de suhipercortisolismo después de la cirugía.Conclusiones: ABL es un procedimiento de rescateeficaz para controlar los síntomas asociados al hipercortisolismo en pacientes con SCE refractario al tratamiento médico.(AU)

Objectives: The aim of this paper is todescribe the clinical features and the perioperative results of the bilateral laparoscopic adrenalectomy (BLA) ofsalvaje in 5 patients treated for an Ectopic Cushing Syndrome (CS) who were refractory to medical treatment.Material and methods: We performed a retrospective analysis of the clinical records of our institution.Five BLAs were performed in patients with Ectopic CSrefractory to medical treatment during the period fromJanuary 2009 and June 2017. All patients were evaluated by a multidisciplinary team that jointly decidedthe most appropriate time for surgery. The followingprotocol data were analyzed: age, sex, location of the secreting tumor, duration of hypercortisolism, reason forhospitalization, initial therapeutic management), biochemical data (pre-op serum cortisol, plasma ACTH andfree urinary cortisol), surgical data (surgical approach,surgical time, type of surgery, need for conversion toopen surgery), perioperative data (post op surgical stay,post op complications according to the Clavien-Dindoscale 14, mortality, clinical cure rate and biochemicalcure rate, follow up time).Results: Five patients underwent BLA. The approachfor the BLA was minimally invasive, either trans peritoneal (n=3) or posterior retroperitoneoscopic (n=2). Meanhospitalization time was 23.4 days (r=4-81). None ofthe patients died because of surgical complications, andall of them achieved biochemical and clinical remissionof their hypercortisolism after surgery.Conclusions: BLA is an effective salvage alternativeto control the symptoms associated with overproductionof corticosteroids in patients with ectopic CS refractoryto medical treatment.(AU)

Asunto(s)

RESUMEN

Ectopic ACTH syndrome (EAS) accounts for 10-20% of endogenous Cushing's syndrome (CS). Hardly any cases of adrenal medullary hyperplasia have been reported to ectopically secrete adrenocorticotropic hormone (ACTH). Here we describe a series of three patients with hypercortisolism secondary to ectopic production of ACTH from adrenal medulla. Cushingoid features were absent in case 1 but evident in the other two cases. Marked hypokalemia was found in all three patients, but hyperglycemia and osteoporosis were present only in case 2. All three patients showed significantly elevated serum cortisol and 24-h urinary cortisol levels. The ACTH levels ranged from 19.8 to 103.0pmol/L, favoring ACTH-dependent Cushing's syndrome. Results of bilateral inferior petrosal sinus sampling (BIPSS) for case 1 and case 3 confirmed ectopic origin of ACTH. The extremely high level of ACTH and failure to suppress cortisol with high dose dexamethasone suppression test (HDDST) suggested EAS for patient 2. However, image studies failed to identify the source of ACTH secretion. Bilateral adrenalectomy was performed for rapid control of hypercortisolism. After surgery, cushingoid features gradually disappeared for case 2 and case 3. Blood pressure, blood glucose and potassium levels returned to normal ranges without medication for case 2. The level of serum potassium also normalized without any supplementation for case 1 and case 3. The ACTH levels of all three patients significantly decreased 3-6 months after surgery. Histopathology revealed bilateral adrenal medullary hyperplasia and immunostaining showed positive ACTH staining located in adrenal medulla cells. In summary, our case series reveals the adrenal medulla to be a site of ectopic ACTH secretion. Adrenal medulla-originated EAS makes the differential diagnosis of ACTH-dependent Cushing's syndrome much more difficult. Control of the hypercortisolism is mandatory for such patients.

Asunto(s)

RESUMEN

OBJECTIVES: The aim of this paper is to describe the clinical features and the perioperative results of the bilateral laparoscopic adrenalectomy (BLA) of salvaje in 5 patients treated for an Ectopic Cushing Syndrome (CS) who were refractory to medical treatment. MATERIALS AND METHODS: We performed a retrospective analysis of the clinical records of our institution. Five BLAs were performed in patients with Ectopic CS refractory to medical treatment during the period from January 2009 and June 2017. All patients were evaluated by a multidisciplinary team that jointly decided the most appropriate time for surgery. The following protocol data were analyzed: age, sex, location of the secreting tumor, duration of hypercortisolism, reason for hospitalization, initial therapeutic management), biochemical data (pre-op serum cortisol, plasma ACTH and free urinary cortisol), surgical data (surgical approach, surgical time, type of surgery, need for conversion toopen surgery), perioperative data (post op surgical stay, post op complications according to the Clavien-Dindo scale 14, mortality, clinical cure rate and biochemical cure rate, follow up time). RESULTS: Five patients underwent BLA. The approach for the BLA was minimally invasive, either trans peritoneal (n=3) or posterior retroperitoneoscopic (n=2). Mean hospitalization time was 23.4 days (r=4-81). None of the patients died because of surgical complications, and all of them achieved biochemical and clinical remission of their hypercortisolism after surgery. CONCLUSIONS: BLA is an effective salvage alter native to control the symptoms associated with overproduction of corticosteroids in patients with ectopic CS refractory to medical treatment.

OBJETIVO: Describir las características clínicas y los resultados perioperatorios de la adrenalectomía bilateral laparoscópica (ABL) en 5 pacientes tratados con diagnóstico de Síndrome de Cushing Ectópico (SCE).MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo y descriptivo de todos los pacientes con SCE sometidos a una ABL, entre enero de 2009 y junio de 2017. Todos los pacientes fueron evaluados por un equipo multidisciplinario que decidió conjuntamente el momento más adecuado para la cirugía. Fueron analizados los siguientes datos protocolares: edad, sexo, origen del tumor secretor, duración del hipercortisolismo, motivo de internación, manejo terapéutico inicial, datos bioquímicos (cortisol sérico preoperatorio, ACTH plasmática y cortisol libre urinario), datos quirúrgicos (vía de abordaje, tiempo quirúrgico, tipo de cirugía, necesidad de conversión a cirugía abierta), datos perioperatorios (tiempo de internación postoperatoria, complicaciones según la escala de Clavien-Dindo, mortalidad, tasa de curación clínica y tasa de curación bioquímica, tiempo de seguimiento). RESULTADOS: Cinco pacientes fueron sometidos a ABL. El abordaje fue mínimamente invasivo, ya sea transperitoneal (n=3) o retroperitoneoscópico posterior (n=2). El tiempo de internación fue de 23,4 días (r=4-81). Ningún paciente falleció por complicaciones quirúrgicas, y todos lograron la curación bioquímica y clínica de su hipercortisolismo después de la cirugía. CONCLUSIONES: ABL es un procedimiento de rescate eficaz para controlar los síntomas asociados al hipercortisolismo en pacientes con SCE refractario al tratamiento médico.

Asunto(s)

RESUMEN

OBJECTIVE: Nelson syndrome (NS) is a rare clinical disorder that can occur after total bilateral adrenalectomy (TBA), performed as a treatment for Cushing disease. NS is defined as the accelerated growth of an adrenocorticotropic hormone-producing pituitary adenoma. Our objective is to describe a case of NS and discuss it based on existing knowledge of this syndrome. METHODS: We describe the case of a woman diagnosed with NS at our facility in the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran and review published cases of NS. RESULTS: The patient, a 35-year-old woman with Cushing disease, had been diagnosed in 2006 at the endocrinology department in the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. In 2007, a laparoscopic TBA was performed, and 2 years later, she presented with hyperpigmentation and adrenocorticotropic hormone levels of up to 11 846 pg/mL. NS was suspected, and as magnetic resonance imaging showed macroadenoma, transsphenoidal surgery was performed. The patient remained asymptomatic until 2012, when she presented with a right hemicranial headache, photophobia, and phonophobia. A fresh magnetic resonance imaging was performed, which documented tumor growth. She was referred to the Instituto Nacional de Neurologia y Neurocirugia, where she underwent surgery. CONCLUSION: NS develops as a complication of TBA, which is used as a treatment of Cushing disease. The main treatment is surgery and radiotherapy.

RESUMEN

PURPOSE: Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. DATA SOURCES: Systematic literature search in four databases. STUDY SELECTION: Observational studies reporting the prevalence of NS after BA in adult patients with CD. DATA EXTRACTION: Data extraction and risk of bias assessment were performed by three independent investigators. DATA SYNTHESIS: Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. CONCLUSIONS: Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.

Asunto(s)

RESUMEN

BACKGROUND: Nelson's syndrome is a rare but challenging sequelae of Cushing's disease (CD) after bilateral adrenalectomy (BLA). We sought to determine if stereotactic radiosurgery (SRS) of residual pituitary adenoma performed before BLA can decrease the risk of Nelson's syndrome. METHODS: Consecutive patients with CD who underwent BLA after non-curative resection of ACTH secreting pituitary adenoma and had at least one follow-up visit after BLA were studied. Nelson's syndrome was diagnosed based on the combination of rising ACTH levels, increasing volume of the pituitary adenoma and/or hyperpigmentation. RESULTS: Fifty patients underwent BLA for refractory CD, and 43 patients (7 men and 36 women) had at least one follow-up visit after BAL. Median endocrine, imaging, and clinical follow-up were 66 months, 69 months, and 80 months, respectively. Nine patients (22%) were diagnosed with the Nelson's syndrome at median time after BLA at 24 months (range: 0.6-119.4 months). SRS before BLA was associated with reduced risk of the Nelson's syndrome (HR = 0.126; 95%CI [0.022-0.714], p=0.019), while elevated ACTH level within 6 months after BLA was associated with increased risk for the Nelson's syndrome (HR = 9.053; 95%CI [2.076-39.472], p=0.003). CONCLUSIONS: SRS before BLA can reduce the risk for the Nelson's syndrome in refractory CD patients requiring BLA and should be considered before proceeding to BLA. Elevated ACTH concentration within 6 months after BLA is associated with greater risk of the Nelsons' syndrome. When no prior SRS is administered, those with a high ACTH level shortly after BLA may benefit from early SRS.

Asunto(s)

RESUMEN

BACKGROUND: Although transsphenoidal adenomectomy is the first treatment choice for Cushing's disease (CD), tumor recurrence rates are as high as 45%, resulting in a therapeutic challenge for endocrinologists and neurosurgeons. For recurrent/persistent CD (RCD/PCD), Repeat transsphenoidal surgery (RTSS), radiotherapy, gamma knife radiosurgery (GKRS) or bilateral adrenalectomy may be considered. The purpose of the study was to report the treatments and outcomes of RCD/PCD in a single center. METHODS: A retrospective study was performed on 55 RCD/PCD patients from a single center between 2000 and 2012 at Peking Union Medical College Hospital (PUMCH). RESULTS: Among the 55 RCD/PCD patients, 43 achieved remission (78%), and 11 maintained a PCD status (20%). The average times to recurrence after the initial treatment and Repeated treatment were 43.25±10.3 and 5.13±4.7 months, respectively (P=0.006); 17.6% of the patients experienced recurrence within the first year, and 52.9% of the patients experienced recurrence within 1.1-5.0 years. For the Repeated treatments, surgery was more effective for the biochemical remission of serum cortisol and adrenocorticotrophic hormone (ACTH) levels than radiotherapy. Delayed remission occurred in 28.9% (11/38) of the patients after Repeated surgery. Considering the previous biochemical levels after the initial surgery in RCD patients, 19.75% of patients experienced recurrence when serum cortisol levels were less than <3 µg/dL, and 51.4% of patients experienced recurrence under conditions of hypocortisolism and when 24-hour urinary free cortisol (24 UFC) was undetectable. CONCLUSIONS: RTSS remains a recommended treatment option for RCD/PCD patients while radiotherapy is suggested as an adjunctive treatment. Intensive follow-up is recommended, as patients with serum cortisol levels <3 µg/dL or undetectable 24 UFC levels can still experience recurrence after surgical treatment.

Asunto(s)

RESUMEN

PURPOSE: Nelson's syndrome (NS) is a long-term complication of bilateral adrenalectomy in patients with Cushing's disease. The best therapeutic strategy in NS has not been well defined. Gamma knife radiosurgery (GKRS) is very effective to stop the growth of the pituitary adenoma, which is the main goal of the treatment of patients with NS. We report the largest series of patients with NS treated by GKRS at a single center. METHODS: The study was an observational, retrospective analysis of 28 consecutive patients with NS treated by GKRS in our department between 1995 and 2019. All patients had a growing ACTH-secreting pituitary adenoma. The main outcome of the study was to assess by the Kaplan-Meier method the risk of tumor progression after GKRS. RESULTS: The median follow-up after GKRS treatment was 98 months (IQR 61-155 months, range 7-250 months). Two patients (7.1%) had a recurrence of disease during follow-up. The 10-year progression-free survival was 91.7% (95% CI 80.5-100%). No patient had deterioration of visual function or oculomotor function after GKRS. New onset of hypogonadism and hypothyroidism occurred in 18.8% and 14.3% of the patients at risk. CONCLUSION: Our study confirms that GKRS may stop the tumor growth in the majority of patients with NS, even though very aggressive adenomas may ultimately escape this treatment. Safety of GKRS was good in our experience, but due attention must be paid to planning the distribution of radiation to critical structures, especially in patients previously treated by radiation.

Asunto(s)

RESUMEN

BACKGROUND: Endogenous Cushing syndrome (CS) can be caused by ectopic corticotropin-producing tumors of known (EK) and unknown origin (EU). Bilateral adrenalectomy (BA) can be used as definite treatment of hypercortisolism in such cases. This study compared patients undergoing BA for CS secondary to EK vs EU. METHODS: Retrospective review (1995-2017) of patients undergoing BA due to EK or EU. We analyzed demographic characteristics, laboratory values, intraoperative variables, surgical outcomes, and survival. RESULTS: 48 patients (26 EU, 22 EK) were identified. Serum cortisol and ACTH concentrations were similar. 92% of BA for EU were performed minimally invasively vs 77% for EK, P = 0.22. Complications occurred in 19% of EU and 4.5% EK, P = 0.2. Mean survival was 4.3 years for EU and 4.0 years for EK without difference in all-cause mortality P = 0.63. CONCLUSION: BA cure rate was 100% for CS in EU and EK. Morbidity, long term and all-cause mortality differences were not statistically significant between EK and EU.

Asunto(s)