Endocrine Abstracts

Background

Cushing’s syndrome due to ectopic ACTH secretion only accounts for 10% of all cases of Cushing’s syndrome and is most often associated with pulmonary neuro-endocrine tumors. Treatment of ectopic ACTH syndrome is predominantly surgical with resection of the tumor. Following resolution of hypercortisolism, previously subclinical Pneumocystis jiroveci infection can become overt due to restored immune response.

Clinical Case

A 37 year old male was referred to the endocrinology outpatient clinic by his general physician with suspicion of secondary hypertension. Initial clinical evaluation revealed a Cushingoid appearance. Laboratory test results, including 24 h urine analysis, showed hypokalemia, elevated urinary free cortisol and elevated serum ACTH. MRI of the pituitary gland revealed absence of pituitary adenoma. Inferior petrosal sinus sampling suggested ectopic ACTH production. CT of the thorax and abdomen, followed by 68Ga-DOTANOC scan, was revealed a tumor in the right lower pulmonary lobe as the probable source of the ectopic ACTH production. Patient underwent surgical resection of the tumor with anatomopathological confirmation of typical carcinoid tumor with low proliferative index. Five days after surgery, patient presented to the emergency department with fever, dyspnea and a dry cough. Arterial blood gas analysis showed type I respiratory failure. Extensive bilateral peribronchial ground-glass opacities were seen on CT thorax. Laboratory test results showed important inflammation with elevated leucocyte count with neutrophilia and an elevated CRP. Patient was initially empirically started on intravenous amoxicillin/clavulanic acid antibiotic therapy and supportive treatment consisting of oxygen therapy and low molecular weight heparin. SARS-CoV-2 PCR on nasopharyngeal swab was negative. Bronchoscopy with broncho-alveolar lavage was performed with a positive PCR for Pneumocystis jiroveci. The diagnosis of bilateral Pneumocystis pneumonia (PCP), following resolution of an ectopic ACTH syndrome, was made. Amoxicillin/clavulanic acid was replaced by trimethoprim/sulfamethoxazole with favorable clinical evolution. A few months later patient is doing well and is almost fully recovered.

Clinical Lesson

Following resolution of hypercortisolism in Cushing’s syndrome, subclinical Pneumocystis jiroveci infection can evolve into fulminant PCP due to immune reconstitution. During prolonged immune suppression, fungal lung burden of Pneumocystis jiroveci may accumulate, with development of extensive inflammatory reaction after abrupt decrease of cortisol levels. Especially in patients with ectopic Cushing syndrome the risk of developing PCP following surgical resection is considerable. Therefore timely chemoprophylaxis with trimethoprim/sulfamethoxazole must be considered in each patient treated for Cushing syndrome.