Doença de cushing e hipertensão arterial: relato de caso / Cushing disease and hypertension: a case report

Caso clínico de VNS, 23 anos, sexo feminino, branca, solteira, estudante, natural e procedente de São Paulo- SP com queixa de "pressão alta" há 4 anos. A paciente foi encaminhada para consulta ambulatorial após ter sido atendida em pronto-socorro (PS) com cefaleia, tonturas e pressão arterial (PA) 210x110 mm Hg e medicada com losartana 50 mg a cada 12 horas e hidroclorotiazida 25 mg ao dia. Na avaliação ambulatorial relatava episódios prévios de cefaleia holocraniana de forte intensidade, latejante, de início gradual há 4 anos com piora há 2 anos, que a levava ao pronto-socorro (PS) com muita frequência. Além disso, referia aumento de peso e fraqueza generalizada. Ao exame físico apresentava-se com níveis elevados da PA 160x100 mm Hg em uso das medicações prescritas no PS, obesidade grau III (IMC 41), adiposidade localizada (giba), acantose nigricans e estrias violáceas abdominais. Foi diagnosticada a doença de Cushing associada à hipertensão arterial não controlada, realizados ajustes dos agentes anti-hipertensivos (associado anlodipino 5 mg a cada 12 horas) e solicitados exames laboratoriais. A monitorização ambulatorial da PA (MAPA) de 24 horas caracterizou a hipertensão resistente, as dosagens de cortisol (cortisol salivar = 8h:172; após 23h:280, supressão com dexametasona =<2,5) e a ressonância nuclear magnética evidenciou um macroadenoma da hipófise confirmando o diagnóstico da doença de Cushing com base nos achados do exame físico, laboratorial e de imagem. A paciente foi tratada clinicamente com cetoconazol via oral sem sucesso e após isso submetida a ressecção transesfenoidal do macroadenoma de hipófise. Após o tratamento cirúrgico, houve perda de peso e resolução da hipertensão confirmada pelas medidas ambulatoriais de consultório e pela MAPA.

Clinical case of VNS, 23 years old, female, white, single, student, born and living in São Paulo-SP, complaining of "high blood pressure" 4 years ago. The patient was referred to an outpatient clinic after being seen in the emergency room (ER) with headache, dizziness and blood pressure (BP) 210x110 mm Hg and medicated with losartan 50 mg every 12 hours and hydrochlorothiazide 25 mg daily. In the outpatient evaluation, she reported previous episodes of severe, throbbing holocranial headache, which started gradually over 4 years and worsened over 2 years ago, which took her to the ER very often. In addition, she reported weight gain and generalized weakness. On physical examination, he presented with high BP levels 160x100 mm Hg using the medications prescribed in ER, obesity grade III (BMI 41), localized adiposity (gib), acanthosis nigricans and abdominal violet streaks. Cushing's syndrome was diagnosed associated with uncontrolled arterial hypertension, adjustments were made to antihypertensive agents (associated with amlodipine 5 mg every 12 hours) and laboratory tests were requested. 24-hour ambulatory BP monitoring (ABPM) characterized resistant hypertension, cortisol levels (salivary cortisol = 8:00 am: 172; after 11:00 pm: 280, dexamethasone suppression = <2.5) and magnetic resonance imaging revealed a macroadenoma of the pituitary gland confirming the diagnosis of Cushing's disease based on the findings of the physical, laboratory and imaging exam. The patient was clinically treated with oral ketoconazole and underwent transphenoid resection of the pituitary macroadenoma. After the surgery the patient was no longer hipertensive, without use of antihypertensive medications, outpatient office measurements were normal, as were measurements outside the office by ABPM

Hipercortisolismo subclínico / Subclinical hypercortisolism

El hipercortisolismo subclínico se define como una alteración del eje hipotálamo hipófisis adrenal en ausencia de los síntomas y signos clásicos del exceso de cortisol. Es una enfermedad endocrina que se presenta hasta en 20 por ciento de los pacientes a los cuales se les diagnostica un tumor adrenal. Las investigaciones realizadas, sugieren la hipótesis que puede estar asociado a complicaciones crónicas como la hipertensión arterial, la diabetes mellitus, el sobrepeso/obesidad y la osteoporosis. El diagnóstico y tratamiento del hipercortisolismo subclínico se han convertido actualmente en un tema de creciente interés y debate, pero aún no existe consenso. Se necesitan estudios prospectivos y aleatorizados para confirmar la hipótesis propuesta, establecer la mejor forma de realizar el diagnóstico y de seleccionar los pacientes que se beneficien con el tratamiento quirúrgico(AU)

Subclinical hypercortisolism is an alteration of the hypothalamus-hypophysis-adrenal axis in absence of classical symptoms and signs of excessive cortisol. It is an endocrine disease that affects up to 20 percent of patients diagnosed with an adrenal tumor. The research studies indicate the hypothesis that this entity could be associated to chronic complications such as blood hypertension, diabetes mellitus, overweight/obesity and osteoporosis. The diagnosis and treatment of subclinical hypercortisolism has turned into a topic of growing interest and discussion nowadays, but the consensus is still pending. It is then necessary to perform prospective and randomized studies in order to confirm the suggested hypothesis, to determine the best way of making a diagnosis and to select the patients who are going to really benefit from a surgical treatment(AU)

Comparisons between Macroadenomas and Microadenomas in Cushing's Disease: Characteristics of Hormone Secretion and Clinical Outcomes

It has been suggested that the patients with Cushing's disease secondary to pituitary macroadenomas (>10 mm) have higher basal adrenocorticotropic hormone (ACTH) levels, which are less suppressible on high-dose dexamethasone suppression tests (HDDST). We compared the clinical and biochemical characteristics of patients with macroadenomas (N=7) and microadenomas (N=23) who were diagnosed at Samsung Medical Center in Korea between 1996 and 2006. Basal morning plasma ACTH levels were 101.5+/-23.2 pg/mL for macroadenoma patients and 83.6+/-11.1 pg/mL for microadenoma patients (mean+/-SEMs) (p=0.44). Morning serum cortisol levels were 26.8+/-3.2 microgram/dL for macroadenoma patients and 29.5 +/-2.9 microgram/dL for microadenoma patients (p=0.77). The proportion of patients who showed suppressibility on HDDST was almost identical in the two groups (71.4% [5/7] for macroadenoma patients vs. 72.7% [16/22] for microadenoma patients, p=1.00). Furthermore, the remission rate with trans-sphenoidal surgery was similar between the two groups (100% [5/5] for macroadenoma patients vs. 73.3% [11/ 15] for microadenoma patients, p=0.53). Thus, tumor size is not a major determinant of hormone secretion or clinical outcomes in patients with Cushing's disease.

Pediatric Cushing's syndrome: clinical features, diagnosis, and treatment: [review]

Cushing's syndrome (CS) results from prolonged exposure to supraphysiological levels of circulating glucocorticoids, endogenously or exogenously derived. Although rare in childhood, CS remains a difficult condition to diagnose and treat. A multidisciplinary approach and close collaboration with adult colleagues is adopted at most large centres that manage pediatric CS patients. Although pediatric protocols are derived from adult data, significant differences exist between adult and childhood CS. Furthermore, long term outcome parameters including final height, bone mineral density, reproductive function, body composition and psychological health pose challenges for pediatric care. This article will aim to provide an overall view of pediatric CS highlighting some of the differences between adult and pediatric CS.

A síndrome de Cushing (SC) resulta da exposição prolongada a níveis suprafisiológicos de glicocorticóides circulantes, tanto endógenos como de seus derivados exógenos. Embora rara na infância, a SC permanece uma condição difícil de ser diagnosticada e tratada. Uma avaliação multidisciplinar e a colaboração próxima com colegas da área não-pediátrica são adotadas na maioria dos grandes centros que cuidam de pacientes pediátricos com SC. Embora os protocolos pediátricos sejam derivados de dados em adultos, existem diferenças significativas entre a SC no adulto e na infância. Além disso, parâmetros evolutivos finais, incluindo altura final, densidade mineral óssea, função reprodutiva, composição corporal e saúde psicológica trazem desafios no cuidado pediátrico. Este artigo procura oferecer uma visão geral da SC pediátrica, focalizando algumas das diferenças entre a SC adulta e a pediátrica.

Cushing's disease: management outcome in a tertiary care centre.

Cushing's syndrome (CS) can pose a challenge in diagnosis and management. Successful management of CS needs accurate localization of the site of lesion. Present article narrates experience of a single center dealing with large number of patients with CS and highlights difficulties in diagnosis as well as management of Cushing's disease (CD). METHODS: All patients with CD, where histopathological lesion was documented were studied to evaluate yield from different diagnostic tests. Diagnosis was established by standard 2 days low dose dexamethasone suppression test. Localization of the lesion was achieved with high dose dexamethasone suppression (HDDS) and imaging. Inferior petrosal sinus sampling (IPSS) was used whenever diagnosis was not arrived at with the standard tests. RESULTS: Out of 100 consecutive patients of CS seen, 69 had CD. HDDS had sensitivity of 70% and specificity of 99% in localizing the lesion. Imaging localized the lesion in 68% of patients. Combination of HDDS and imaging localized the lesion in 90% of patients. IPSS helped to localise the lesion in remaining 10% of patients. Transsphenoidal surgery was carried out in 65/69 patients. Cure rate for microadenoma was 77% and for macroadenoma was 36%. Mortality and morbidity rate was 7% and 7% respectively. 2nd TSS, radiotherapy and bilateral adrenalectomy were the additional modalities used in that order, in patients who were not cured or who had recurrence. CONCLUSION: Management of CS is best carried in a center where a team of experienced endocrinologist and neurosurgeon is available.