Differential diagnosis of ACTH-dependent Cushing's syndrome: a case report

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 306-326-Neoplasia of Endocrine Tissues: Case Reports
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-313
Marina Cunha Silva*1, Tassiane Cintra Alvarenga Oliveira1, Ludmila Malveira1, Marcio Carlos Machado2, Marcello D Bronstein2 and Maria Candida Barisson Villares Fragoso3
1Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, 2Disciplina de Endocrinologia e Metabologia, Unidade de Neuroendocrinologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil., 3Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo

Background: Diagnosis of Cushing’s syndrome (CS) involves a step-wise approach, and establishing the cause can be challenging in some cases. Aim: To describe the diagnostic evaluation of a patient with suspected CS. Case: A 23-year-old female with recent onset of hypertension presented fatigue and weight gain of 10kg over the last six months. She denied using  steroids. Physical examination revealed cushingoid appearance, BP 130/90mmHg, centrally obese. Laboratory: ACTH:57 (reference< 45pg/dL) midnight salivary cortisol (F), late evening serum F, and 24-hr urinary F repeatedly elevated, morning serum F did not suppress after overnight 1mg dexamethasone. Differential diagnosis of ACTH-dependent CS Desmopressin (DDAVP) test revealed 128% (response>20%) and 318% (response>35%) of the increase in F and ACTH, respectively. hCRH test did not show a significant response, with an increase of ACTH and F respectively 24.3% (response>105%) and 4.5% (response>14%). Pituitary MRI showed a 0.4cm nodule in the right paramedian region. Chest CT showed an indeterminate 0.8cm nodule in the middle lobe. Abdominal CT, OctreoScan and FDG-PET do not suggest abnormalities. Tumor markers AFP, CEA, gastrin, calcitonin, CA15.3, CA 19.9, and β-hCG were in normal range. Due to divergent results of the DDAVP and hCRH tests, and the inconclusive imaging in pituitary gland, the bilateral inferior petrosal sinus sampling (BIPSS) was held under stimulus of DDAVP, for differentiation between Cushing's disease (CD) and ectopic ACTH syndrome (EAS). The center/periphery ACTH gradient (C/P) was suggestive of EAS. Due to diagnosis of EAS and also the increase of size of lung tumor, the patient underwent resection of the pulmonary nodule. The histological study showed a carcinoid tumour with immunostaining positive for ACTH. After surgery, patient developed secondary adrenal insufficiency, confirming the diagnosis of EAS. Discussion Etiologic diagnosis of CS remains a challenge in clinical practice and performing dynamic testing often becomes necessary. We report a case with a high clinical PPV of CD considering the patient’s gender and age, identification of pituitary nodule and DDAVP test. The DDAVP test has not showed good accuracy in the differential diagnosis of ACTH-dependent CS, because patients with EAS could respond due to the presence of V2 and V3 receptors in these tumors. For this purpose, CRH test revealed greater accuracy, but its low availability and high costs limit its use. Nonetheless both ACTH secretagogues are useful in amplification of the C/P gradient in BIPSS, which is considered the gold standard method for the differential diagnosis of ACTH-dependent CS.

Nothing to Disclose: MCS, TCAO, LM, MCM, MDB, MCBVF

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