Endocrine Abstracts

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a relatively recent and rare disease, frequently misdiagnosed. It is characterized as a generalized proliferation of pulmonary neuroendocrine cells and is recognized as a precursor lesion for pulmonary neuroendocrine tumors, although the risk of progression to malignancy is considered low. Here we report a patient with ectopic ACTH-dependent Cushing’s syndrome due to metastatic lung carcinoid tumors arising on a background of DIPNECH. A 73-year-old woman presented to the emergency department with 4 weeks of progressive lower limb edema, sudden onset of hypokalemia, refractory hypertension and de novo diabetes. She had basilar crackles on auscultation and hepatomegaly on examination. Past medical history included controlled hypertension, obesity, dyslipidemia. She was being followed in Pulmonology for chronic cough and radiological findings suggestive of DIPNECH. A thoracic CT showed diffuse mosaic attenuation with multiple bilateral lung nodules, with the largest nodules measuring 8 mm. Biopsy of the pulmonary nodules demonstrated tumorlet/typical carcinoid tumor, with evidence of DIPNECH. Severely elevated GGT prompted a cholangio-MRI that showed heterogeneous/micronodular liver parenchyma suggestive of chronic liver disease. Liver biopsy demonstrated hepatic involvement by a well differentiated neuroendocrine neoplasia expressing chromogranin and synaptophysin with a proliferative index Ki67 < 2%, compatible with metastasis. The patient became increasingly confused and disoriented over the first days of hospitalization. In view of clinical suspicion of endogenous hypercortisolism, screening for Cushing’s syndrome was performed. She had elevated elevated morning and midnight plasma cortisol levels (58.0 and 83.4 µg/dl, respectively) markedly increased 24-hour urinary free cortisol (3648.0 µg/day) and morning serum ACTH (167.1 ng/l). High-dose dexamethasone suppression test revealed no suppression of urinary free cortisol. A PET-Ga-68-DOTATOC was obtained showing multiple tumor lesions located at the cervical, thoracic and abdominal ganglia, lung (identified as the primary source), bone and liver with overexpression of somatostatin receptors. A PET-FDG-F18 excluded the presence of concomitant dedifferentiated/high grade metabolic lesions. Therapy with octreotide and metyrapone was initiated with a prompt and sustained decrease in serum and urinary cortisol levels. At hospital discharge, the patient was fully oriented, with controlled cortisol and potassium levels. Her vital signs were normal and peripheral edema was mild and limited to the ankles. Six months after discharge she remained clinically and imagiological stable under somatostatin analogs and metyrapone. This case describes disease progression from DIPNECH to metastatic carcinoid tumours presenting with ectopic Cushing’s, highlighting the importance of long term clinical surveillance in patients with DIPNECH.