Endocrine Abstracts

Ectopic Cushing’s syndrome is a rare condition accounting for 10–20% of all cases of ACTH-dependent Cushing. Neuroendocrine tumours (NETs), mainly bronchial carcinoids and small cell lung cancer, are the most frequent causes of ectopic ACTH secretion(1). Here we report two challenging cases with long duration of surveillance and monitoring.

Case 1: A 42-year-old lady with a florid Cushing syndrome underwent bilateral adrenalectomy in 2002. An IPSS in 2001 failed to demonstrate a central to peripheral ACTH gradient suggesting an ectopic ACTH secretion. Serial whole-body gallium 68 DOTATATE PET CT over a decade failed to reveal any tracer avid lesion. CT CAP did not identify any pathology. Since 2012, her ACTH level continued to rise and peaked at 3800 ng/l. Despite thorough radiological evaluation, the source remained unlocalised. In 2016, 16 years after her initial diagnosis, her CT CAP revealed a 13 mm right perihilar nodule with a positive FDG-PET in the perihilar region. She underwent right middle lobectomy. Histology showed a typical bronchial carcinoid with positive ACTH stain and low proliferation index (Ki-67 1%). Post operative ACTH level was 12 ng/l and she is in remission.

Case 2: A 31 years old lady was diagnosed with ectopic Cushing’s syndrome and required bilateral adrenalectomy in 1990 to ameliorate hypercortisolism. Surveillance imaging with CT and octreotide scans over the period showed two right lung nodules with marginal interval growth. The case was discussed in the lung MDT in 2006 and 2014. The nodules were not amenable for surgery. Her ACTH level during this time was between 1000 and 2800 ng/l. In 2015, the nodules increased in size with growth noted in proximity to the main vessels and bronchi. It was then decided to proceed with a right lung wedge resection. Histology confirmed bronchial carcinoids and stained positive for ACTH. The ACTH level fell from peak 2210 to 24 ng/l postoperatively with spontaneous remission of Cushing’s syndrome.

Conclusion : We present two uncommon cases of ectopic ACTH secretion caused by bronchial carcinoid, which took nearly two decades for localisation. The cases highlight the fact that identifying the source of ectopic secretion is always challenging due to their small size and unpredictable anatomical location. It is of paramount importance for regular follow up with surveillance imaging.

Reference: 1. Young, J. et al. (2020) Management of endocrine disease: Cushing’s syndrome due to ectopic ACTH secretion: An expert operational opinion, eje. Bioscientifica Ltd. (https://eje.bioscientifica.com/view/journals/eje/182/4/EJE-19-0877.xml)