Ectopic ACTH Secretion (EAS) Associated to a Well-Differentiated Peritoneal Mesothelioma

Case Report

Carmen F. Mendoza; Patricia Ontiveros; Daniel X. Xibillé; Manuel H. Rivera

Disclosures

BMC Endocr Disord. 2015;15(40) 

In This Article

Case Presentation

The patient is a 43 years old hispanic female with a history of left leg monoparesis as a complication of poliomyelitis. She was nubile, menarche occurred at age 14 and she initially had regular cycles. She was diagnosed with diabetes mellitus and hypertension at age 22, requiring treatment with 3 antihypertensive drugs in order to reach a stable control and used NPH insulin plus metformin for metabolic control; consequently, she has been diagnosed with non proliferative diabetic retinopathy and proteinuria. She underwent a diagnostic protocol for suspected Cushing's disease 13 and 5 years prior to her visit to our center in two tertiary care centers, one of which performed an inferior petrosal sinus catheterization; the origin of the syndrome was never identified and the patient ceased going to subsequent appointments.

She was seen for the first time at our center 3 years prior; she came to the clinic complaining of polymenorrhea which had started 18 months prior, she had a full moon face, a buffalo hump, increased volume in both supraclavicular regions, purple striae in her arms and abdomen, truncal obesity, an umbilical hernia, decreased muscle mass of the pelvic limbs, uncontrolled glycemia, hypertension, albuminuria, a decreased glomerular filtration rate of 35 ml/min and osteoporosis. We performed the diagnostic protocol for Cushing's syndrome again, as indicated in international guidelines; diagnostic tests showed the following data: urinary free cortisol: 186.5 μg/day, AM serum cortisol 21.83 μg/dL and midnight serum cortisol 16.09 μg/dL, serum cortisol post-1 mg dexamethasone (Low dose dexamethasone suppression test, LDDST): 16.6 μg/dL [all performed by chemiluminescent assay (CL), Accesses Immunoassay Systems], plasma ACTH: 32.6 pg/mL (CL), baseline AM serum cortisol: 17.8 μg/dL (CL), an overnight high-dose (8 mg PO) dexamethasone suppression test: 2.69 μg/dL (CL); TSH: 2.62 mIU/mL (0.50 to 5.0), free T4: 0.70 ng/dL (0.58 to 1.64) and free T3: 2.72 pg/mL (2.39 to 6.79); Total T4: 6.42 mg/dL (6.09 to 12.23) and Total T3: 0.88 ng/mL (0.87 to 1.78) [CL, Accesses immunoassay systems]. An MRI was performed in two different tertiary care centers due to the HDDST suppression percentage (84.8 %), both reporting a normal pituitary. Abdominal computed tomography (CT) showed a bilobed image with protrusion through the umbilicus, with attenuation coefficients of 3, 7 and 45 HU; after administration of contrast enhancement they reached 6, 16 and 88 HU, with a size of 68x60x76 mm. Multiplanar reconstructions showed that its origin was intra-abdominal, adjacent to a loop of small intestine, and the possibility of a mesothelioma was considered (Fig. 1). Images suggestive of uterine fibroids were also observed. Ultrasound imaging showed a normal liver, gallbladder and kidneys, with an enlarged uterus due to uterine fibroids and both ovaries showing no evidence of tumor or cystic lesions. The case was discussed with the General Surgery and Gynecology departments, and abdominal surgery was performed. The findings were: uterus with fibroids, abundant ascites and tumor implants in the omentum, bladder, bowel, ovaries and appendix. An intraoperative biopsy reported an ovarian carcinoma. A total hysterectomy, bilateral oophorectomy, omentectomy, appendectomy and umbilical hernioplasty was performed. The tumor implants were not completely removed due to the magnitude of their peritoneal extension. Finally, the pathology department, after analyzed the resected tissue, concluded that the patient had a well-differentiated papillary mesothelioma through staining with immunohistochemistry (Fig. 2).

Figure 1.

Abdominal computed tomography (CT) showed a bilobed image with protrusion through the umbilicus, with attenuation coefficients of 3, 7 and 45 HU; after administration of contrast enhancement they reached 6, 16 and 88 HU. Multiplanar reconstructions showed that its origin was intra-abdominal, adjacent to a loop of small intestine, and the possibility of a mesothelioma was considered

Figure 2.

Immunohistochemistry. (a) A biopsy specimen showing a papillary pattern of the tumor and the absence of mitosis. (b)There is diffuse positivity for ACTH. Biopsy specimen positive to Calretinin (c) y thrombomodulin (d), supporting the diagnosis of mesothelioma

Twenty four hours after surgery, her AM serum cortisol was measured (20.9 μg/dL). A month later the urinary free cortisol was 143.6 μg/day and serum cortisol post-1 mg dexamethasone was 19.1 μg/dL.

She is currently treated with ketoconazole 400 mg once a day, baseline insulin, calcium antagonists, statins, omega 3 fatty acids and conjugated estrogens. Despite not being cured, the patient does not want further treatment or any more invasive procedures. Her most recent laboratory results are: Plasma glucose 87 mg/dL, total cholesterol 145 mg/dL, triglycerides 172 mg/dL, HDL cholesterol 66.3 mg/dL, LDL cholesterol 73 mg/dL, creatinine 1.3 mg/dL, BUN 30 mg/dL and glycated hemoglobin 5.3 %.

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