Guía colombiana de práctica clínica para el diagnóstico y tratamiento del incidentaloma adrenal / Colombian clinical practice guideline for diagnostic and treatment of adrenal incidentaloma

Objetivo: Brindar recomendaciones actualizadas a urólogos y profesionales de la salud involucrados en el diagnóstico y manejo del incidentaloma adrenal. Métodos: Mediante la adopción de la guía para manejo de incidentaloma adrenal de la Sociedad Europea de Endocrinología (AGREE-II y AGREE-REX) y búsqueda complementaria de literatura basada en la mejor evidencia científica disponible en definición, diagnóstico, manejo quirúrgico y seguimiento. Adicionalmente, esta guía aborda pacientes con incidentalomas bilaterales y embarazadas. Resultados: Incidentaloma adrenal se define como una lesión mayor de 1 cm localizado en la suprarrenal, detectada mediante una imagen realizada por una razón diferente a cualquier sospecha de patología adrenal. La gran mayoría son adenomas no funcionantes, que no representan riesgo y no requieren manejo adicional. Sin embargo, existen lesiones tumorales como el carcinoma adrenocortical, el feocromocitoma, adenomas productores de hormonas o metástasis. Conclusiones: Los incidentalomas adrenales son masas predominantemente benignas que no requieren adrenalectomía, no obstante se requiere estudiarlas para descartar patologías que requieran manejo específico. Enfáticamente, la intervención quirúrgica debe guiarse por la probabilidad de malignidad, grado de secreción hormonal, edad, estado de salud y preferencia del paciente.

Objective: To provide updated recommendations to urologists and health-care providers faced to diagnosis and treatment of adrenal incidentaloma. Methods: Through adoption of the adrenal incidentaloma guideline from European Endocrinology Society (AGREE-II and AGREE-REX), and complementary search of literature based on available high-quality scientific evidence for definition, diagnosis, surgical management and follow-up. Additionally, this guideline covers bilateral adrenal incidentalomas and pregnant women. Results: Adrenal incidentaloma is defined as a lesion greater than 1 cm localized in adrenal gland, detected by imaging studies which are requested for another different reason than an adrenal pathology suspicion. A great majority are non-functional adenomas, without life-threatening risk nor additional treatment necessity. However, there are tumoral lesions that demand appropriate management like adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma, or metastasis. Conclusions: Adrenal incidentalomas predominantly are benign masses that do not require adrenalectomy (specially in asymptomatic, unilateral, non-functioning adrenal mass), nevertheless, must be exclude other harmful pathologies. Emphatically, surgical treatment must be indicated by malignant probability, hormonal-secreting status, age, health condition, and patient's preference.

Resistant Hypertension: A Clinical Case / Hipertensión resistente: un caso clínico / Hipertensão resistente: um caso clínico

Abstract Introduction: Secondary hypertension corresponds to 15 % of the causes of arterial hypertension, and among them, primary hyperaldosteronism presents a variable incidence of about 3 % in hypertensive patients. It has a slightly higher prevalence in women, between 30 and 60 years, and is usually unilateral. Case presentation: The authors describe the clinical case of a patient, followed by a severe hypertension medicated with four antihypertensive drugs for tension stabilization, maintaining systolic arterial tensions superior to 170 mmHg. In the aetiological study of hypertension, analytical alterations suggested hyperaldosteronism and a nodular lesion was detected in the left adrenal gland. The patient was submitted to surgery and excision of the lesion was done with histological confirmation of the diagnosis of corticomedullary adenoma of the adrenal gland. The patient presented improvement of the tension profile, with need to suspend two of the four antihypertensive drugs and to reduce the dose of the remaining ones. Conclusion: A tumor of the adrenal cortex producing aldosterone is the main cause of primary hyperaldosteronism and should always be excluded when the presence of difficult to control, severe hypertension is detected, since the standard treatment is surgical, leading to a stabilization of the tension pattern after a few months.

Resumen Introducción: la hipertensión secundaria corresponde al 15 % de las causas de hipertensión arterial, y entre ellas, el hiperaldosteronismo primario presenta una incidencia variable de sobre 3 % en pacientes hipertensos. Tiene una prevalencia ligeramente mayor en mujeres, entre 30 y 60 años, y generalmente es unilateral. Presentación del caso: los autores describen el caso clínico de un paciente, seguido por una hipertensión resistente medicada con cuatro fármacos antihipertensivos para la estabilización de la tensión, con mantenimiento de las tensiones arteriales sistólicas superiores a 170 mmHg. Las alteraciones analíticas en el estudio etiológico de la hipertensión sugirieron hiperaldosteronismo y una lesión nodular en la glándula suprarrenal izquierda. El paciente fue sometido a cirugía y se realizó la escisión de la lesión con confirmación histológica del diagnóstico de adenoma corticomedular de la glándula suprarrenal. El paciente presentó una mejora en el perfil de tensión, con la necesidad de suspender dos de los cuatro fármacos antihipertensivos y reducir la dosis de los restantes. Discusión: un tumor de la corteza suprarrenal que produce la aldosterona es la principal causa de hiperaldosteronismo primario y siempre debe excluirse cuando se presenta hipertensión grave, difícil de controlar, ya que el tratamiento estándar es quirúrgico y conduce a una estabilización del patrón de tensión después de unos meses.

Resumo Introdução: a hipertensão secundária corresponde ao 15 % das causas de hipertensão arterial, e entre elas, o hiperaldosteronismo primário apresenta uma incidência variável de sobre 3 % em pacientes hipertensos. Tem uma prevalência ligeiramente maior em mulheres, entre 30-60 anos, e geralmente é unilateral. Apresentação do caso: os autores descrevem o caso clínico de um paciente, seguido por uma hipertensão resistente medicada com quatro fármacos anti-hipertensivos para a estabilização da tensão, com manutenção das tensões arteriais sistólicas a 170 mmHg. As alterações analíticas no estudo etiológico da hipertensão sugeriram hiperaldosteronismo e uma lesão nodular na glândula suprarrenal esquerda. O paciente foi submetido a cirurgia e se realizou a incisão da lesão com confirmação histológica do diagnóstico de adenoma córtico-medular da glândula suprarrenal. O paciente apresentou uma melhora no perfil de tensão, com a necessidade de suspender dois dos quatro fármacos anti-hipertensivos e reduzir a dose dos restantes. Discussão: um tumor do córtex suprarrenal que produz a aldosterona é a principal causa de hiperaldosteronismo primário e sempre deve excluir-se quando se apresenta hipertensão grave, difícil de controlar, pois o tratamento standard é cirúrgico e conduz a uma estabilização do patrão de tensão depois de uns meses.

Síndrome de Cushing adrenal dependiente de hormona luteinizante / Luteinising hormone-dependent Cushing's syndrome

La hormona luteinizante (LH) y la gonadotropina coriónica humana (hCG) puede inducir esteroidogénesis, hiperplasia y tumorigénesis adrenal a través del estímulo sobre el receptor constitutivo de la LH (R-LHCG) en la corteza adrenal. Los mecanismos fisiopatológicos del síndrome de Cushing adrenal dependiente de LH (SCa-LH) no se han establecido plenamente, pero es reconocida la relación ontogénica adrenal-gonadal con mutua participación de diversos genes, factores de transcripción y enzimas esteroidogénicas como posible causa. El SCa-LH fue descrito en mujeres durante la gestación por el estímulo de hCG y en la posmenopausia ante el aumento de LH, así como en hurones luego de la gonadectomía quirúrgica.

Luteinising hormone (LH) and human chorionic gonadotropin (hCG) can induce steroidogenesis, hyperplasia, and adrenal tumorigenesis through the stimulus of the constitutive LH receptor (R-LHCG) within the adrenal cortex. The pathophysiological mechanisms of luteinising hormone-dependent Cushing's syndrome are not completely understood, but the ontogenic relationship between the adrenal cortex and the gonads, with mutual participation of different genes, transcription factors and steroidogenic enzymes cited as a possible cause, is well-recognised. SCa-LH has been described in pregnant women, as a result of hCG stimulus, and in post-menopausal women, due to increased levels of LH, as well as in ferrets after gonadectomy.

Síndrome de Cushing durante el embarazo: manifestaciones cutáneas secundarias a un tumor suprarrenal / Cushing's syndrome secondary to adrenal tumor during pregnancy

El síndrome de Cushing secundario a tumor suprarrenal es una patología infrecuente en el embarazo. Su presencia se traduce en un aumento significativo de la morbimortalidad materna y fetal. Muchas de sus características clínicas son enmascaradas por los cambios propios de una gestación fisiológica, lo que dificulta el diagnóstico. En este contexto las manifestaciones dermatológicas pueden ser de gran utilidad en la sospecha clínica precoz. Se presenta el caso de una paciente de 26 años de edad que en el segundo trimestre de embarazo inicia un cuadro caracterizado por acné inflamatorio severo e hirsutismo. La gestación se interrumpe a las 35 semanas por síndrome hipertensivo del embarazo y rotura prematura de membranas. Durante el puerperio consulta al dermatólogo presentando aún las lesiones descritas, además de estrías violáceas gruesas en abdomen, facie de luna, obesidad centrípeta y máculas purpúricas en zonas de presión. Se diagnóstica síndrome de Cushing. El estudio confirmatorio y etiológico dirigido evidenció un adenoma de corteza suparrenal. El diagnóstico de laboratorio es difícil debido a los cambios físicos y de laboratorio habituales del embarazo que pueden mimetizar los hallazgos propios de la enfermedad. Los hallazgos dermatológicos pueden ser de gran valor para un diagnóstico y tratamiento precoz. Las lesiones dermatológicas secundarias al hipercortisolismo fueron de difícil manejo...

Cushing's syndrome secondary to adrenal tumor is a rare pathology in pregnancy. Its presence results in a significant increase in maternal and fetal morbimortality. Many of its clinical features are masked by the typical changes of a physiological pregnancy, which make difficult the diagnosis. Indeed, skin manifestations may be useful in early clinical suspicion. We report a case of a 26 year old in the second trimester with severe inflammatory acne and hirsutism. The pregnancy is interrupted at 35 weeks for pregnancy-induced hypertension syndrome and premature rupture ovular membranes. During the puerperium, patient consulted a dermatologist presenting still the injuries described, as well as thick purple striae throughout the abdomen, moon face, truncal obesity and purpuric macules in pressure zones. Cushing's syndrome is diagnosed. The study showed a cortex suprarenal adenoma. Laboratory diagnosis is difficult because the pregnancy physical changes and routine laboratory findings that can mimic the disease themselves. Dermatological findings may be valuable for diagnosis and early treatment. The skin lesions secondary to hypercortisolism were difficult to manage...

Hipertensão arterial, osteoporose, amenorreia e depressão como manifestações da síndrome de cushing acth-independente: evolução após adrenalectomia laparoscópica / Arterial hypertension, osteoporosis, amenorrhea, and depression as presentation of ACTH-independent Cushing's syndrome: follow-up after laparoscopic adrenalectomy

A síndrome de Cushing é caracterizada por excesso de glicocorticóides circulantes. Os tumores suprarrenais secretores de cortisol representam a principal causa desse distúrbio, dentre os quais adenomas, que correspondem a 65% dos casos. A apresentação clínica típica inclui obesidade centrípeta, fadiga, hipertensão arterial de difícil controle, osteoporose, distúrbios menstruais, hirsutismo, equimoses e estrias violáceas. Entretanto, casos de síndrome de Cushing subclínica vem sendo descritos com frequência crescente, o que faz com que essa doença ainda representardesafio diagnóstico na atualidade, pela capacidade de mimetizar outras entidades nosológicas, tais como síndrome metabólica, depressão e alcoolismo. Relata-se o caso de uma mulher de 27 anos, que vinha em tratamento de hipertensão arterial, osteoporose e depressão intensa antes do diagnóstico de síndrome de Cushing ACTH-independente,na qual o tratamento cirúrgico da doença de base resultou abrandamento significativo das comorbidades.

Cushing’s syndrome is characterized by an excess of circulating glucocorticoids. Cortisol-secreting adrenal tumors are the most common cause of endogenous ACTH-independent disease, with adrenal adenomas accounting for 65% of these cases. The typical clinical presentation includes centripetal obesity, fatigue, arterial hypertension, osteoporosis, menstrual disorders, hirsutism, easy bruising, and diffuse violaceous striae. However, subclinical Cushing´s syndrome is being described with growing frequency, still making this disease a diagnostic challenge, due to the ability to mimicother nosologic entities, such as the metabolic syndrome, depression and alcoholism. The authors report the case of a 27-year-old woman, who has been treated for hypertension, osteoporosis and depression before the diagnosis of ACTH-independent Cushing’s syndrome was established, and in whom the surgical treatment of the disease resulted in significant improvement of co-morbidities.

Subclinical Cushing's syndrome: [review]

Subclinical Cushing's syndrome (CS) is attracting increasing interest since the serendipitous discovery of an adrenal mass has become a rather frequent event owing to the routine use of sophisticated radiologic techniques. Cortical adenoma is the most frequent type of adrenal incidentaloma accounting for approximately 50 percent of cases in surgical series and even greater shares in medical series. Incidentally discovered adrenal adenomas may secrete cortisol in an autonomous manner that is not fully restrained by pituitary feedback, in 5 to 20 percent of cases depending on study protocols and diagnostic criteria. The criteria for qualifying subclinical cortisol excess are controversial and presently there is no consensus on a gold standard for the diagnosis of this condition. An increased frequency of hypertension, central obesity, impaired glucose tolerance, diabetes and hyperlipemia has been described in patients with subclinical CS; however, there is still no clear demonstration of the long-term complications of this condition whose management remains largely empirical. Either adrenalectomy or careful observation associated with treatment of the metabolic syndrome have been suggested as treatment options.

A síndrome de Cushing subclínica (SCS) tem atraído interesse cada vez maior desde que a descoberta casual de uma massa adrenal se tornou um evento freqüente devido ao emprego rotineiro de técnicas sofisticadas de imagem. O adenoma cortical é o tipo mais freqüente de incidentaloma adrenal, correspondendo a cerca de 50 por cento dos casos em séries cirúrgicas e até mais do que isso em séries médicas. Adenomas adrenais descobertos incidentalmente podem secretar cortisol de maneira autônoma ou não controlada totalmente pelo feedback hipofisário, em 5 a 20 por cento dos casos, dependendo do protocolo de estudo e dos critérios diagnósticos. Os critérios para qualificar um excesso subclínico de cortisol são controversos e atualmente não existe consenso a respeito de "padrão ouro" para o diagnóstico dessa condição. Em pacientes com SCS, tem sido descrita uma freqüência elevada de hipertensão, obesidade central, intolerância à glicose, diabetes e hiperlipemia; entretanto, ainda não existe uma evidente demonstração de complicações a longo prazo dessa condição, cujo manejo permanece amplamente empírico. Tanto a adrenalectomia como a observação cuidadosa, associada com o tratamento da síndrome metabólica, têm sido sugeridos como opções terapêuticas.

Cushing's syndrome in pregnancy: an overview: [review]

Cushing's syndrome (CS) during pregnancy is a rare condition with fewer than 150 cases reported in the literature. Adrenal adenomas were found to be the commonest cause, followed by Cushing's disease. The gestation dramatically affects the maternal hypothalamic-pituitary-adrenal axis, resulting in increased hepatic production of corticosteroid-binding globulin (CBG), increased levels of serum, salivary and urinary free cortisol, lack of suppression of cortisol levels after dexamethasone administration and placental production of CRH and ACTH. Moreover, a blunted response of ACTH and cortisol to exogenous CRH may also occur. Therefore, the diagnosis of CS during pregnancy is much more difficult. Misdiagnosis of CS is also common, as the syndrome may be easily confused with preeclampsia or gestational diabetes. Because CS during pregnancy is usually associated with severe maternal and fetal complications, its early diagnosis and treatment are critical. Surgery is the treatment of choice for CS in pregnancy, except perhaps in the late third trimester, with medical therapy being a second choice. There does not seem to be a rationale for supportive treatment alone.

A ocorrência de síndrome de Cushing (SC) durante a gravidez é rara, com menos de 150 casos reportados na literatura. Os adenomas adrenais parecem ser a causa mais comum seguidos da doença de Cushing. A gestação afeta de maneira dramática o eixo hipotálamo-hipófise-adrenal materno resultando em aumento da produção hepática da globulina ligadora de corticosteróides (CBG), aumento dos níveis séricos, salivares e livres urinários de cortisol, falta de supressão do cortisol após administração de dexametasona e produção placentária de CRH e ACTH. Além disso, pode também ocorrer bloqueio da resposta do ACTH e do cortisol ao CRH exógeno. Assim, o diagnóstico de SC durante a gravidez torna-se muito mais difícil. A falha em diagnosticar SC é também comum, já que a síndrome pode ser facilmente confundida com pré-eclampsia ou diabetes gestacional. Uma vez que a SC de ocorrência na gravidez é usualmente associada com graves complicações materno-fetais, seu diagnóstico e tratamento precoces tornam-se críticos. A cirurgia é o tratamento de escolha para a SC na gravidez, exceto, talvez, no final do 3º trimestre, sendo o tratamento medicamentoso a segunda escolha. Não parece haver nenhum arrazoado para o tratamento de suporte isoladamente.

Adrenal venous sampling in the differential diagnosis of primary aldosteronism / 中国实用内科杂志

Objective To study the value of adrenal venous sampling (AVS) in the differential diagnosis of primary aldosteronism (PA).Methods Fourteen patients (11 adenoma and 3 adrenal hyperplasia) clinically diagnosed as PA were examined with AVS for measurement of plasma aldosterone and cortisol levels.Selectivity of AVS was assessed by the aldosterone level in each adrenal vein and in the infrarenal inferior vena cava plasma.The data were compared with CT and postoperative pathologic result.Results The diagnosis of adenoma by AVS in 9 (9/11) cases was in accordance with the postoperative pathologic findings.The diagnosis of hyperplasia by AVS in all 3 cases was in accordance with CT scanning result.Conclusion AVS should be selected to distinguish the PA without overt occupational lesion in CT scanning.

The characteristics of the gene expression and its associated molecular mechanism of one case with Cushing′ssyndrome(adrenalcorticoadenoma) / 中华内分泌代谢杂志

Objective To explore the characteristics of the gene expression in Cushing′s adrenal corticoadenoma and its associated molecular mechanism. Methods cDNA libraries of human normal adrenal and the adenoma were constructed. Large scale sequencing and bioinformatics were used. Results From the tumor library, 2089 expressed sequence tags (ESTs) were obtained with a successful rate of 98.9%. The functional distribution of the known genes in the tumor coincided with that in normal adrenal. Some synthases such as 3bHSDⅡ and P450c17A involved in steroidogenesis were expressed more highly in the adenoma than those in normal adrenal, especially 3bHSDⅡ. By comparison with the expression abundance of genes and statistic analysis, the differences were significant in 45 genes between the tumor and normal adrenal libraries. Interestingly, some genes associated with tumorigenesis, including heat shock protein 90, metallopanstimulin (MPS1), adenine nucleotide translocators etc, were highly expressed in the adenoma. However, those genes related to apoptosis and suppressing proliferation were not found in the tumor library. Conclusion The adenoma shows exuberant activities in steroid synthesis. Not only does the tumor highly express the genes associated with tumorigenesis, but also those related to apoptosis and suppressing proliferation lowly existed in the tumor.