Enfermedad de Cushing recurrente con hipercortisolismo catastrófico: reporte de caso y revisión de literatura / Catastrophic hypercortisolism and recurrence in Cushing´s disease: a case report and literature review / Doença de Cushing recorrente com hipercortisolismo catastrófico: relato de caso e revisão da literatura

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.

Effects of comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome / 中华烧伤杂志

Objective: To investigate the characteristics and comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome. Methods: A retrospective observational study was conducted. From May 2012 to December 2021, the data of 19 patients with iatrogenic Cushing's syndrome discharged from the Department of Burns and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University were collected, including 8 males and 11 females, aged 28-71 (56±11) years, with 12 cases of infected acute wounds and 7 cases of infected chronic wounds. The lesions were located in the limbs, perianal, and sacrococcygeal regions, with original infection ranging from 9 cm×5 cm to 85 cm×45 cm. After admission, the patients were performed with multidisciplinary assisted diagnosis and treatment, and the wounds were treated with debridement and vacuum sealing drainage, according to the size, severity of infection, suture tension, and bone and tendon tissue exposure of wounds, direct suture or autologous skin and/or artificial dermis and/or autologous tissue flap transplantation was selected for wound repair. The levels of cortisol and adrenocorticotropic hormone (ACTH) of patients at 8:00, 16:00, and 24:00 within 24 h after admission were counted. After admission, the number of operations, wound repair methods, and wound and skin/flap donor site healing of patients were recorded. During follow-up, the wounds were observed for recurrent infection. Results: The cortisol levels of 16 patients at 8:00, 16:00, and 24:00 within 24 h after admission were (130±54), (80±16), and (109±39) nmol/L, respectively, and ACTH levels were (7.2±2.8), (4.1±1.8), and (6.0±3.0) pg/mL, respectively; and the other 3 patients had no such statistical results. After admission, the number of surgical operation for patients was 3.4±0.9. The following methods were used for wound repair, including direct suturing in 4 cases and autologous skin and/or artificial dermis grafting in 9 cases, of which 2 cases underwent stage Ⅱ autologous skin grafting after artificial dermis grafting in stage Ⅰ, and 6 cases had pedicled retrograde island flap+autologous skin grafting. The wound healing was observed, showing that all directly sutured wounds healed well; the wounds in 6 cases of autologous skin and/or artificial dermis grafting healed well, and the wounds in 3 cases also healed well after the secondary skin grafting; the flaps in 4 cases survived well with the wounds in 2 cases with distal perforators flap arteries circumfluence obstacle of posterior leg healed after stage Ⅱ debridement and autologous skin grafting. The healing status of skin/flap donor sites was followed showing that the donor sites of medium-thickness skin grafts in the thigh of 4 cases were well healed after transplanted with autologous split-thickness grafts from scalp; the donor sites of medium-thickness skin grafts in 3 cases did not undergo split-thickness skin grafting, of which 2 cases had poor healing but healed well after secondary skin grafting 2 weeks after surgery; the donor sites of split-thickness skin grafts in the head of 2 patients healed well; and all donor sites of flaps healed well after autologous skin grafting. During follow-up of more than half a year, 3 gout patients were hospitalized again for surgical treatment due to gout stone rupture, 4 patients were hospitalized again for surgical treatment due to infection, and no recurrent infection was found in the rest of patients. Conclusions: The infected wounds in patients with iatrogenic Cushing's syndrome have poor ability to regenerate and are prone to repeated infection. Local wound treatment together with multidisciplinary comprehensive treatment should be performed to control infection and close wounds in a timely manner, so as to maximize the benefits of patients.

Adrenalectomía laparoscópica / Laparoscopic adrenalectomy

Introducción: desde el año 1997 se comenzó a realizar la adrenalectomía laparoscópica en nuestro centro. Objetivo: analizar los resultados de la adrenalectomía laparoscópica desde su implementación en el servicio de cirugía general del Hospital Clínico Quirúrgico Hermanos Ameijeiras. Métodos: Se realizó un estudio descriptivo de los resultados obtenidos en 160 pacientes a los que se les realizó adrenalectomía por vía laparoscópica, en el período comprendido desde noviembre de 1997 hasta septiembre del año 2017 en el servicio de cirugía general del Hospital Clínico Quirúrgico Universitario Hermanos Ameijeiras. Se empleó la técnica laparoscópica con abordaje lateral intraperitoneal en la mayoría de los casos y el abordaje en decúbito supino en 2 casos para la adrenalectomía bilateral. Resultados: se realizaron 162 adrenalectomías laparoscópicas en 160 pacientes, ya que a dos pacientes se les realizó la adrenalectomía bilateral en un tiempo. La edad promedio fue de 44,8 años. La indicación quirúrgica fue el incidentaloma en 68 pacientes (42,5 pr ciento), el síndrome de Cushing en 27 (16,8 por ciento), feocromocitoma en 26 (16,25 por ciento), la Enfermedad de Cushing con fracaso del tratamiento neuroquirúrgico en 12 (7,5 por ciento), mielolipomas en 7 (4,37 por ciento), tumor adrenal en 6 (3,75 por ciento), tumor metastásico en 5 (3,1 por ciento), quistes adrenales en 4 (2,5 por ciento), hiperaldosteronismo primario en 3 (1,87 por ciento), tumor virilizante adrenal en 1 paciente y 1 paciente con un Síndrome de secreción ectópica de ACTH que le provocaba un Síndrome de Cushing complicado. Predominaron las lesiones del lado izquierdo en 86 pacientes, 72 del lado derecho y 2 bilaterales. Fueron convertidos a cirugía convencional 2 pacientes (1,25 por ciento). El tiempo quirúrgico promedio fue de 82 minutos. La estadía posoperatoria promedio fue de 2.5 días. Conclusiones: la adrenalectomía laparoscópica es una técnica reproducible y segura con las ventajas inherentes a la cirugía laparoscópica(AU)

Introduction: As far as 1997, the performing of laparoscopic adrenalectomy started in our center. Objective: To analyze the results of laparoscopic adrenalectomy since its implementation in the general surgery service of Hermanos Ameijeiras Clinical Surgical Hospital. Methods: A descriptive study was carried out with the results obtained from 160 patients who underwent laparoscopic adrenalectomy, in the period from November 1997 to September 2017, in the general surgery service of Hermanos Ameijeiras University Clinical Surgical Hospital. The laparoscopic technique with intraperitoneal lateral approach was used in the majority of cases and the supine approach was used in two cases for bilateral adrenalectomy. Results: 162 laparoscopic adrenalectomies were performed in 160 patients, since two patients underwent bilateral adrenalectomy at one time. The average age was 44.8 years. Surgical indication cases were incidentalomas, in 68 patients (42.5 percent), Cushing's syndrome in 27 (16.8 percent), pheochromocytomas in 26 (16.25 percent), Cushing's disease with neurosurgical treatment failure in 12 (7.5 percent), myelolipomas in 7 (4.37 percent), adrenal tumor in 6 (3.75 percent), metastatic tumor in 5 (3.1 percent), adrenal cysts in 4 (2.5 percent), primary hyperaldosteronism in 3 (1.87 percent), adrenal virilizing tumor in 1 patient, and 1 patient with an ectopic ACTH secretion syndrome that caused a complicated Cushing's syndrome. Lesions on the left side were predominant in 86 patients, 72 on the right side and two bilateral. Two patients (1.25 percent) were converted to conventional surgery. The average surgical time was 82 minutes. The average postoperative stay was 2.5 days. Conclusions: Laparoscopic adrenalectomy is a reproducible and safe technique with the advantages inherent to laparoscopic surgery(AU)

Long-term Results after CT-Guided Percutaneous Ethanol Ablation for the Treatment of Hyperfunctioning Adrenal Disorders

OBJECTIVES: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyperfunctioning adrenal disorders. METHOD: We retrospectively evaluated the long-term results of nine patients treated with computed tomography-guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macronodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment. Eleven sessions were performed for the nine patients. The patient data were reviewed for the clinical outcome and procedure-related complications over ten years. RESULTS: Patients with aldosterone-producing adenoma had clinical improvement: symptoms recurred in one case 96 months after ethanol ablation, and the other patient was still in remission 110 months later. All patients with pheochromocytoma had clinical improvement but were eventually submitted to surgery for complete remission. No significant clinical improvement was seen in patients with hypercortisolism due to primary macronodular adrenal hyperplasia or Cushing disease. Major complications were seen in five of the eleven procedures and included cardiovascular instability and myocardial infarction. Minor complications attributed to sedation were seen in two patients. CONCLUSION: Computed tomography-guided ethanol ablation does not appear to be suitable for the long-term treatment of hyperfunctioning adrenal disorders and is not without risks.

Síntomas psicóticos, paranoides y catatónicos como debut de enfermedad de Cushing en una paciente con síndrome de Turner: reporte de caso y revisión de la literatura / Psicotic, paranoid and catatonic symptoms as Cushing disease onset in a Turner syndrome patient: case report and literature revision

It is known that hipercortisolism and overactivity of the Hypotalamus pituitary adrenal axis are associated to psiquiatric diseases presentation. In patients with Cushing syndrome, mood disorders are common, also psicosis cases also are present during the disease. But, the presence and mostly the onset with a episode of catatonic psicosis is unusual. The cortisol excess produce structural damage in the Central Nervous System, reversible and irreversible, specially in the hypocampus. We show the case of a young woman with previous diagnostic of Turner syndrome, karyotype 45 X0, who presented a psychiatric episode caracterized for depresive psicotic symptoms and posteriorly a catatonic state as an unusual form of Cushing disease onset. This patient presented health improvement after pituitary resection. There is not evidencia that Turner syndrome influes over this unusual form of presentation.

Se conoce que el hipercortisolismo y la sobreactividad del eje hipotálamo pituitario adrenal están asociados a la presentación de enfermedades psiquiátricas. En pacientes con síndrome de Cushing son frecuentes los trastornos del ánimo aunque también se presentan casos de psicosis durante el curso de la enfermedad. Sin embargo es inusual la presencia y más aún el debut con un cuadro de psicosis catatónica. El exceso de cortisol produce daño estructural en el sistema nervioso central tanto reversible como irreversible, especialmente en el hipocampo. Presentamos el caso de una paciente mujer joven con diagnóstico previo de síndrome de Turner, cariotipo 45 X0, quien presentó un cuadro psiquiátrico caracterizado por síntomas depresivos psicóticos y posteriormente catatonia como forma inusual de debut de enfermedad de Cushing y presentó mejoría posterior a la resección de la pituitaria. No se tiene evidencia que el síndrome de Turner influya sobre esta rara forma de presentación.

Caso clí­nico: reactivación de psoriasis posterior a adrenalectomía por sí­ndrome de Cushing / Case report: psoriasis relapse following adrenalectomy for cushing syndrome

The relapse of autoimmune diseases following resolution of Cushing syndrome (CS) has been established with frequency, especially for thyroid disease. We present the case of a 39-year-old woman with a history of psoriasis vulgaris, with no other comorbidities. She presented a one-year of weight gain, high blood pressure, hypermenorrhea, pre-diabetes and dyslipidemia. During this period of time, the complete remission of psoriatic lesions was confirmed. The laboratory analysis demonstrated elevated free urinary cortisol in two opportunities, and a confirmatory low-dose dexamethasone test. Low ACTH levels were established (12,3pg/ml), and the abdominal images where compatible with a right adrenal adenoma of 3,0 x 2,3 cm, sothe patient underwent a laparoscopic right adrenalectomy with no complications. Her blood pressure, glucose and cholesterol levels improved following surgery. One month after surgery the patient developed new, generalized psoriatic plaques. The excess of glucocorticoids produced by the adrenal tumor could have controlled the immunopathogeny of psoriasis. By removing the tumor, with the consequent reduction of cortisol levels, a more severe relapse of her cutaneous disease occurred.

Transumbilical Single Port Laparoscopic Adrenalectomy: A Technical Report on Right and Left Adrenalectomy Using the Glove Port

Recently, single port laparoscopic surgery has been the focus of attention due to the advanced laparoscopic skills accumulated from experience and developments in laparoscopic instruments. Herein, we present two cases of initial single port laparoscopic adrenalectomies. Case 1 was a 38-year-old female patient diagnosed with primary hyperaldosteronism because of a the right adrenal 2.5-cm sized adenoma, and case 2 was a 31-year-old female patient diagnosed with primary adrenal Cushing's syndrome because of a left adrenal 2.9-cm sized adenoma. Both patients successfully underwent single port laparoscopic adrenalectomies via a transumbilical transperitoneal approach. There was no estimated blood loss and the total operating times were 60 and 70 minutes, respectively. Both patients recovered uneventfully. We believe that this technique presented could provide potential benefits (lesser wound pain, better cosmetic satisfaction, and shorter convalescence) if the indications are carefully selected.

Síndrome de Cushing na gravidez: relato de caso / Cushing syndrome in pregnancy: case report

A ocorrência de síndrome de Cushing (SC) durante a gravidez é rara, com menos de 150 casos reportados na literatura. Este relato demonstra a dificuldade diagnóstica e a gravidade da desordem adrenal específica durante a gestação, assim como a necessidade de diagnóstico e intervenção precoces. Este trabalho apresenta paciente portadora da SC com início das suas manifestações clínicas a partir do terceiro mês de gestação. Foi realizada durante a gestação a investigação bioquímico-laboratorial, que permitiu avaliação clínico-laboratorial e confirmação diagnóstica de SC. O método de imagem empregado foi a ressonância magnética do abdômen. Após a cirurgia por videolaparoscopia, houve redução do peso e dos níveis pressóricos e normalização dos níveis do cortisol plasmático e urinário, além do controle dos níveis glicêmicos.

The occurrence of Cushing Syndrome (CS) in pregnancy is rare, with less than 150 case reports in the literature. This report shows the diagnosis difficulty and the severity of the specific adrenal disorder during pregnancy, as well as the need for precocious diagnosis and intervention. This paper presents a patient with CS starting its physical manifestations from the third gestation month. The biochemical-laboratory survey was carried out during the pregnancy, which allowed the clinic-laboratory evaluation and the CS diagnosis confirmation. The used image method was abdomen magnetic resonance. After surgery by video laparoscopy, there was weight and pressure levels reduction and normalization of plasma cortisol and urinary levels, besides the glycemic levels control.

A laparoscopic versus open adrenalectomy in Ramathibodi Hospital.

OBJECTIVE: To compare the results of laparoscopic adrenalectomy with those of open adrenalectomy in Ramathibodi Hospital. MATERIAL AND METHOD: Medical charts of 41 laparoscopic and 39 open adrenalectomy patients were reviewed Baseline characteristics and outcomes of treatment were compared between these two patient groups, using univariable statistical tests and multivariable statistical procedures. RESULTS: There were significant baseline differences between the two groups in terms of gender, body mass index, ASA class, and preoperative diagnosis. The outcomes operative time, estimated blood loss and length of hospital stay were also significantly different. After adjusting for the effects of baseline differences, laparoscopic adrenalectomy was associated with a significant reduction of length of hospital stay by 40%. CONCLUSION: Laparoscopic adrenalectomy is a safe and effective procedure and should help hasten postoperative recovery and may save the costs of hospitalization.

Role for laparoscopic adrenalectomy in patients with Cushing's syndrome

Laparoscopic adrenalectomy is one of the most clinically important advances in the past 2 decades for the treatment of adrenal disorders. When compared to open adrenalectomy, laparoscopic adrenalectomy is equally safe, effective, and curative; it is more successful in shortening hospitalization and convalescence and has less long-term morbidity. The laparoscopic approach to the adrenal is the procedure of choice for the surgical management of cortisol-producing adenomas and for patients with corticotropin (ACTH) dependent Cushing's syndrome for whom surgery failed to remove the source of ACTH. The keys to successful laparoscopic adrenalectomy are appropriate patient selection, knowledge of anatomy, delicate tissue handling, meticulous hemostasis, and experience with the technique of laparoscopic adrenalectomy.

A adrenalectomia laparoscópica é um dos avanços clínicos mais importantes das últimas duas décadas para o tratamento de doenças adrenais. Quando comparada à adrenalectomia aberta (convencional), a adrenalectomia laparoscópica é igualmente segura, efetiva e curativa; ela tem maior sucesso em encurtar a hospitalização e a convalescença e apresenta menor morbidade a longo prazo. A abordagem laparoscópica da adrenal é o procedimento de escolha para ao manejo cirúrgico dos adenomas produtores de cortisol e para os pacientes com síndrome de Cushing ACTH-dependente nos quais a cirurgia hipofisária falhou em remover a fonte de ACTH. Os pontos críticos para o sucesso da adrenalectomia laparoscópica são: a seleção apropriada do paciente, o conhecimento da anatomia da região, o manuseio cuidadoso do tecido, a homeostase meticulosa e a experiência com essa técnica cirúrgica.

Cushing's syndrome: aftermath of the cure

Cushing's syndrome (CS) is a chronic and systemic disease caused by endogenous or exogenous hypercortisolism, associated with an increase of mortality rate due to the clinical consequences of glucocorticoid excess, especially cardiovascular diseases. After cure, usually obtained by the surgical removal of the tumor responsible for the disease, the normalization of cortisol secretion is not constantly followed by the recovery of the clinical complications developed during the active disease, and it is often followed by the development of novel clinical manifestations induced by the fall of cortisol levels. These evidences were mostly documented in patients with pituitary-dependent CS, after surgical resection of the pituitary tumor. Indeed, despite an improvement of the mortality rate, metabolic syndrome and the consequent cardiovascular risk have been found to partially persist after disease remission, strictly correlated to the insulin resistance. Skeletal diseases, mainly osteoporosis, improve after normalization of cortisol levels but require a long period of time or the use of specific treatment, mainly bisphosphonates, to reach the normalization of bone mass. A relevant improvement or resolution of mental disturbances has been described in patients cured from CS, although in several cases, cognitive decline persisted and psychological or psychiatric improvement was erratic, delayed, or incomplete. On the other hand, development or exacerbation of autoimmune disorders, mainly thyroid autoimmune diseases, was documented in predisposed patients with CS after disease remission. The totality of these complications persisting or occurring after successful treatment contribute to the impairment of quality of life registered in patients with CS after disease cure.

A síndrome de Cushing (SC) é uma desordem sistêmica crônica causada por hipercortisolismo endógeno ou exógeno, associada a um aumento da taxa de mortalidade devido às conseqüências clínicas do excesso de glicocorticóides, especialmente a doença cardiovascular. Após a cura, usualmente obtida pela remoção cirúrgica do tumor responsável pela desordem, a normalização da secreção de cortisol não é sistematicamente seguida da recuperação das complicações clínicas desenvolvidas durante a fase ativa da doença, e é freqüentemente seguida pelo surgimento de novas manifestações clínicas induzidas pela queda dos níveis de cortisol. Estas evidências foram, na sua maioria, documentadas em pacientes com SC de origem hipofisária, após a ressecção cirúrgica do tumor na hipófise. Na verdade, a despeito de uma melhoria na taxa de mortalidade, a síndrome metabólica e seu conseqüente risco cardiovascular têm se mostrado parcialmente persistentes após a remissão da doença, em estrita relação com a resistência à insulina. Anormalidades esqueléticas, especialmente a osteoporose, melhoram após a normalização dos níveis de cortisol, mas requerem um longo tempo ou o uso de tratamento específico, principalmente bisfosfonatos, para se obter a normalização da massa óssea. Uma melhora significativa ou mesmo resolução dos distúrbios mentais têm sido descritos em pacientes curados da SC, embora em vários casos o declínio cognitivo persista e a melhora psicológica ou psiquiátrica tenham sido erráticas, demoradas ou incompletas. Por outro lado, o desenvolvimento ou exacerbação de processos autoimunes, em especial as doenças autoimunes da tiróide, foram documentadas em pacientes predispostos com SC, após a remissão da doença. A totalidade dessas complicações, persistentes ou ocorrendo após o tratamento bem sucedido, contribuem para um prejuízo da qualidade de vida registrado em pacientes com SC após a cura da doença.

Effect of hypercortisolism control on high blood pressure in Cushing's syndrome / Efecto del control del hipercortisolismo sobre la hipertensión arterial en el síndrome de Cushing

Many hypertensive patients affected by endogenous Cushing's syndrome (CS) persist with high blood pressure (HBP) despite good control of cortisol excess. We assessed the effect of preoperative ketoconazole administration and of definitive treatment of CS on arterial hypertension and analysed the factors involved in the persistence of hypertension. We assessed retrospectively 71 patients with CS and HBP (60 women, 11 men; 50 pituitary, 21 adrenal) successfully treated by surgery and/or radiotherapy; 19 of them received ketoconazole (KNZ) before surgery. After treatment, patients were divided into those with persistent high blood pressure (PHBP) and those with normal blood pressure (NBP). As possible predictive factors for PHBP we analysed age, duration and family history of HBP, pre-treatment 24 hour urinary free cortisol (24h-UFC) and body mass index (BMI). HBP normalized in 53 out of 71 patients (74.6%), regardless of the origin of Cushing's syndrome. PHBP patients were older (p=0.003), had longer duration (p=0.007) and higher systolic blood pressure before treatment (p=0.046) than NBP patients. Thirteen out of 19 patients (68.4%) treated with ketoconazole, normalized their hypertension and remained normotensive after successful surgery. Five patients became normotensive only after surgery. In conclusion: a) blood pressure levels normalized in most patients after remission of CS; b) ketoconazole was effective for the control of HBP, and seems to be a good indicator of post-surgical outcome, and c) higher age at presentation, longer duration of hypertension and higher systolic blood pressure figures before treatment negatively influence normalization of blood pressure after resolution of Cushing's syndrome.

Muchos pacientes con síndrome de Cushing (SC) permanecen hipertensos a pesar del control del exceso glucocorticoideo. Investigamos el efecto de la administración de ketoconazol (KNZ) y del tratamiento definitivo del SC sobre la hipertensión arterial (HTA), analizando su relación con diversos factores. Evaluamos 71 pacientes con SC e HTA (60 mujeres, 11 varones; 50 pituitarios, 21 adrenales) exitosamente tratados por cirugía y/o radioterapia; 19 de ellos recibieron KNZ antes de cirugía. Luego del tratamiento, fueron divididos en pacientes con HTA persistente (HTAP) y normal (HTAN). Como posibles factores predictivos de HTAP se analizaron edad, duración, historia familiar de HTA, cortisol libre urinario de 24 hs pre-tratamiento e índice de masa corporal. La HTA normalizó en 53/71 pacientes (74.6%) independientemente del origen del síndrome de Cushing. Los pacientes con HTAP fueron de mayor edad (p=0.003), con mayor duración previa (p=0.007) y valores mayores de presión arterial sistólica antes de tratamiento (p=0.046) que aquellos con HTAN. Trece de 19 pacientes (68.4 %) tratados con ketoconazol normalizaron su tensión arterial y se mantuvieron normotensos luego de cirugía exitosa. Cinco pacientes se tornaron normotensos solo después de cirugía. En conclusión: a) la HTA se normalizó en la mayoría de pacientes luego de remisión del SC, b) el ketoconazol fue efectivo para el control tensional y aparenta ser indicador de la evolución pos-quirúrgica, y c) mayor edad, duración más prolongada de la HTA y valores más altos de presión sistólica influencian negativamente la normalización de la presión arterial luego de resolución del síndrome de Cushing.

Síndrome de Nelson: relato de caso / Nelson's Syndrome: a case report

O objetivo deste artigo é apresentar e discutir alguns aspectos da patogênese, do diagnóstico clínico, hormonal e radiológico e do tratamento da síndrome de Nelson, com base no relato de um paciente típico portador da doença, no qual várias abordagens terapêuticas mostraram-se ineficazes.

The aim of this article is to present and discuss several aspects of the pathogenesis, the clinical, hormonal, and imaging diagnosis, and the treatment of Nelson's syndrome, based on a typical patient's report, in whom several therapeutic approaches were shown to be ineffective.

Ketoconazole therapy: an efficacious alternative to achieve eucortisolism in patients with Cushing's syndrome

El síndrome de Cushing (SC) es un trastorno grave que requiere frecuentemente tratamiento medicamentoso. Cincuenta y cuatro pacientes (44 mujeres, 10 varones) de 14-63 años de edad con SC, recibieron ketoconazol (KTZ) previo a cirugía (n=27), como complemento luego de cirugía y/o radioterapia (n=16), o como tratamiento primario (n=11). La dosis de mantenimiento fue de 600 (500 - 600) mg/día (mediana-IC95) durante 15 días a 13 años. Los signos clínicos, hepatograma y cortisol libre urinario (CLU) fueron evaluados antes y durante tratamiento con KNZ. El CLU cayó a valores normales o subnormales en 85% de los pacientes, 5 a 150 días luego de iniciar el tratamiento; aún sin normalizar, el CLU disminuyó a 12-48% de los valores pre-tratamiento en el resto de los pacientes acompañándose de mejoría de los signos clínicos. Los efectos colaterales fueron: insuficiencia adrenal (18.5%), toxicidad hepática reversible (11%), "rash" cutáneo (5.5%) e intolerancia gástrica (3.7%); en 11% de los pacientes se observó un fenómeno de "escape". Veinticuatro pacientes (44.4%) fueron tratados por períodos prolongados, de uno a trece años. Este estudio confirma que el KTZ constituye un tratamiento eficaz y generalmente bien tolerado del SC, en particular: a) como preparación para cirugía b) en casos de hipercortisolismo residual luego de cirugía o en espera de resultados de radioterapia, c) como una alternativa razonable en pacientes con SC de origen desconocido y, d) como tratamiento crónico en casos de hipercortisolismo no resuelto luego de fracaso de las terapéuticas habituales.

Cushing's syndrome (CS) is a serious condition requiring drug management in diverse clinical settings. Fifty four patients (44 females, 10 males) with CS, aged 14-63, received ketoconazole (KTZ) prior to surgery (n= 27), as complementary therapy after surgery and/or radiotherapy (n= 16), or as primary treatment (n= 11). It was given at a 600 (500 - 600) mg/day (median - CI95) maintenance dose for periods ranging from 15 days to 13 years. Clinical signs, hepatic enzymes and urinary free cortisol (UFC) were evaluated before and during KTZ treatment. UFC normalised or decreased to subnormal values in 85% of the patients, in 5 to 150 days after starting treatment; although failing to normalise, UFC decreased to 12-48% of pre-treatment values in the remaining patients. Clinical signs improved throughout. Side effects were adrenal insufficiency (18.5%), reversible hepatic toxicity (11%), allergic skin rash (5.5%) and gastric intolerance (3.7%); in 11% of patients, an "escape phenomenon" was observed. Twenty-four out of the total (44.4%) were treated for prolonged periods, from one up to 13 years. In conclusion, this study confirms that KTZ is an effective and generally well tolerated treatment for CS particularly: a) shortly before surgery, b) because of persistent hypercortisolism after surgery or awaiting the results of radiotherapy, c) as a reasonable option in patients with CS of unknown aetiology and, d) as long-term therapy in any case of unsolved hypercortisolism after failure of current treatments.

Adrenalectomía laparoscópica en pacientes con síndrome de Cushing / Laparoscopic adrenalectomy in patients with Cushing syndrome

Se describe la experiencia en adrenalectomía laparoscópica en el síndrome de Cushing. Material y Métodos: De una serie total de 214 adrenalectomías laparoscópicas realizadas en nuestra institución entre junio de 1996 y diciembre de 2005, 18 corresponden a síndrome de Cushing. Su edad promedio fue de 36 años, 11 mujeres y 2 hombres, 8 casos unilaterales y 5 casos bilaterales. A todos los pacientes se les realizó la técnica transperitoneal. Resultados: Se realizaron 18 adrenalectomías laparoscópicas en 13 pacientes, con un tiempo quirúrgico promedio de 76,6 min. Fue necesaria la conversión en 1 caso por sangrado intraoperatorio. La estadía hospitalaria en promedio fue de 2,8 días. El tamaño de la glándula en promedio fue de 3,4 cm. En todos los pacientes hubo mejoría clínica y de laboratorio del hipercortisolismo. Conclusión: La adrenalectomía laparoscópica es segura y efectiva para el tratamiento de síndrome de Cushing.

Objectives: To describe and compare our experience in laparoscopic adrenalectomy in Cushing’s syndrome. Material and Methods: Between june 1996 and december 2005 we performed 214 laparoscopic adrenalectomies. From this series, 18 procedures were done in 13 patients with Cushing’s syndrome. The average age at diagnosis was 36. We operated on 11 women and 2 men, eight with unilateral disease and 5 with bilateral disease. Results: Eighteen laparoscopic adrenalectomies were performed; with a mean operative time of 76.6 min. Conversion to open adrenalectomy was necessary in one case to control intraoperative bleeding. Mean hospital stay was 2.8 days. Mean specimen size was 3.4 cm. No major complications were registered. In all cases the resolution of hypercortisolism was then confirmed with clinical and biochemical parameters. Conclusion: In our experience laparoscopic adrenalectomy is safe and effective in the treatment of Cushing’s Syndrome.

Radiocirurgia nos adenomas hipofisários / Radiosurgery for pituitary adenomas / Radiosurgery for pituitary adenomas

Os adenomas hipofisários correspondem a aproximadamente 15 por cento dos tumores intracraniais. As modalidades de tratamento incluem microcirurgia, terapia medicamentosa e radioterapia. A microcirurgia é o tratamento primário realizado nos pacientes com adenomas não-funcionantes e na maioria dos adenomas funcionantes. Dentre estes, a exceção são os prolactinomas, cujo tratamento primário é baseado no uso de agonistas dopaminérgicos. Entretanto, cerca de 30 por cento dos pacientes requerem tratamento adicional após a microcirurgia devido à recorrência ou persistência tumoral. Nesses casos, a radioterapia fracionada convencional tem sido tradicionalmente empregada. Mais recentemente, a radiocirurgia tem se estabelecido com uma alternativa terapêutica. A radiocirurgia permite que a dose prescrita seja precisamente conformada ao volume-alvo, e que se poupe os tecidos adjacentes. Portanto, os riscos de hipopituitarismo, alteração visual e vasculopatia são significativamente menores. Além disso, a latência da resposta à radiocirurgia é substancialmente menor do que na radioterapia fracionada convencional. Nesta revisão, procuramos definir a eficácia, segurança e o papel da radiocirurgia no tratamento dos adenomas hipofisários, bem como apresentar os dados preliminares de nossa instituição.

Pituitary adenomas represent nearly 15 percent of all intracanial tumors. Multimodal treatment includes microsurgery, medical management and radiotherapy. Microsurgery is the primary recommendation for nonfunctioning and most of functioning adenomas, except for prolactinomas that are usually managed with dopamine agonist drugs. However, about 30 percent of patients require additional treatment after microsurgery for recurrent or residual tumors. In these cases, fractionated radiation therapy has been the traditional treatment. More recently, radiosurgery has been established as a treatment option. Radiosurgery allows the delivery of prescribed dose with high precision strictly to the target and spares the surrounding tissues. Therefore, the risks of hypopituitarism, visual damage and vasculopathy are significantly lower. Furthermore, the latency of the radiation response after radiosurgery is substantially shorter than that of fractionated radiotherapy. The goal of this review is to define the efficacy, safety and role of radiosurgery for treatment of pituitary adenomas and to present the preliminar results of our institution.

Primary pigmented nodular adrenocortical disease associated with Carney complex: case report and literature review

CONTEXT: Carney complex (CNC), a familial multiple neoplasm syndrome with dominant autosomal transmission, is characterized by tumors of the heart, skin, endocrine and peripheral nervous system, and also cutaneous lentiginosis. This is a rare syndrome and its main endocrine manifestation, primary pigmented nodular adrenal disease (PPNAD), is an uncommon cause of adrenocorticotropic hormone-independent Cushing's syndrome. CASE REPORT: We report the case of a 20-year-old patient with a history of weight gain, hirsutism, acne, secondary amenorrhea and facial lentiginosis. Following the diagnosing of CNC and PPNAD, the patient underwent laparoscopic bilateral adrenalectomy, and she evolved with decreasing hypercortisolism. Screening was also performed for other tumors related to this syndrome. The diagnostic criteria, screening and follow-up for patients and affected family members are discussed.

CONTEXTO: O complexo de Carney (CNC), uma síndrome de neoplasia múltipla familiar com transmissão autossômica dominante, caracteriza-se por tumores cardíacos, cutâneos, endócrinos e do sistema nervoso periférico, além de lentiginose cutânea. RELATO DE CASO: Devido à raridade da síndrome, bem como de sua principal manifestação endócrina, a doença adrenal nodular pigmentada primária (PPNAD), causa incomum de síndrome de Cushing ACTH-independente, relatamos o caso de uma paciente de 20 anos com história de ganho de peso, hirsutismo, acne, amenorréia secundária e lentiginose em face. Após estabelecido o diagnóstico de CNC e PPNAD, a paciente foi submetida a adrenalectomia bilateral via laparoscópica, evoluindo com melhora do hipercortisolismo. Também foi realizado rastreamento para os demais tumores relacionados à síndrome. Serão discutidos os critérios diagnósticos, o rastreamento e o acompanhamento dos pacientes e familiares afetados.

[Clinical features and treatment in cushing's disease. About 18 cases]

We report a retrospective study about 18 Cushing's diseases colliged in the department of endocrinology at Charles Nicolle hospital in 24 years. The mean age was 33, 7 years with a male-female ratio of 4/14 Diagnosis was established on adrenocorticotropin hormone analysis and pituitary imaging. Transsphenoidal adenomectomy was related in 8 cases of Cushing's disease, it was sussessful in 5 patients [62.5%]. Bilateral adrenalectomy was performed in three cases

Guías para el diagnóstico y tratamiento de acromegalia, prolactinomas y enfermedad de Cushing / Guides for the diagnosis and treatment of acromegally, prolactinoma and disease of Cushing

Los tumores hipofisiarios funcionantes más frecuentes son los productores de prolactina (prolactinomas), hormona del crecimiento (agromegalia) y ACTH (síndrome de Cushing). Existe mucha controversia con respecto al diagnóstico y manejo de estas patologías. Este artículo presenta una guía para el diagnóstico y tratamiento de tales tumores hipofisiarios, y ha sido elaborado por la Asociación Costarricense de Endocrinología, Diabetes y Nutrición. La causa más frecuente de acromegalia son los tumores hipofisiarios productores de hormona de crecimiento. El diagnóstico usualmente se retarda varios años luego de haberse iniciado los cambios, por lo lento que se producen las manifestaciones clínicas. El tratamiento inicial de elección consiste en la cirugía, reservándose tratamiento médico con análogos de somatostatina como primera elección, para casos donde ha fallado el tratamiento quirúrgico. Otra posibilidad de tratamiento consiste en la radioterapia, cuya eficacia se ve limitada por el tiempo necesario para hacer efecto. Con respecto a las hiperprolactinemias, se deben descartar otras causas que produzcan elevación de prolactina. Si se identifica un prolactinoma, el tratamiento va a ser médico en la mayoría de los casos, reservándose la cirugía para aquellos macroprolactinomas con compromiso visual que no han reducido de tamaño con el tratamiento médico. El tratamiento de elección consistió en agonistas dompaminérgicos, y en Costa Rica la elección será bromocriptina, aunque hay otras opciones como cabergolina y quinagolide. En la enfermedad de Cushing existen diferentes pruebas de diagnóstico, tanto para tamizaje como para diagnóstico confirmatorio. El tratamiento inicial debe ser cirugía, seguida por radioterapia. En este caso el tratamiento médico es mucho menos eficaz que en otras dos entidades. Descriptores: acromegalia, prolactinoma, enfermedad de Cushing, guías de tratamiento.