Endocrine Abstracts

We present two uncommon cases of cyclical ectopic ACTH-dependent Cushing’s syndrome due to diffuse idiopathic pulmonary neuroendocrine tumour (DIPNECH).

Case 1: 62 yr lady presented with rapid onset of muscle weakness, diabetes and hypokalaemia. Random cortisol:1710 nmol/l, ACTH level:610 ng/l. LDDST: failure to suppress cortisol levels. Imaging: normal pituitary gland and bilateral adrenal hyperplasia, consistent with ACTH dependent Cushing’s syndrome. She was commenced on Metyrapone. Inferior Petrosal Sinus Sampling (IPSS) was planned and Metryapone withdrawn, however 2/52 off Metyrapone, cortisol and ACTH had normalised, consistent with spontaneous resolution of Cushing’s syndrome. IPSS was postponed. 2/12 later, she again relapsed and Metyrapone was restarted. IPSS confirmed ectopic ACTH source. CT chest showed a right lower lobe nodule, with increased uptake on 68-Gallium DOTATATE PET/CT scan. Prior to resection, she again cycled out of Cushing’s syndrome and therefore, given a Block and replace regime of Metyrapone/HC whilst undergoing Rt lobectomy. Histology showed Carcinoid tumour with evidence of DIPNECH. Post-operatively, she is in remission, requiring continued HC replacement.

Case 2: 33 yr lady presented with a short history of weight gain, abdominal striae, proximal myopathy and secondary amenorrhoea. Of note, she reported a previous episode with similar symptoms one year earlier which subsided spontaneously after a few weeks. Random cortisol:4000 nmol/l, ACTH:98 ng/l. LDDST: failure to suppress cortisol levels. IPSS showed no central:peripheral ACTH gradient, representing ectopic ACTH source. CT chest showed multiple pulmonary nodules, a dominant RLL nodule larger since 2006. 68-Gallium DOTATATE PET/CT scan was normal. Metyrapone was commenced. One week later, Metyrapone was stopped due to low cortisol levels. Off Metyrapone, cortisol levels remained low with concomitant reduction of ACTH levels, indicating another spontaneous remission of Cushing’s syndrome. Histology from an excision biopsy of the RLL nodule revealed tumourlets with a typical carcinoid appearance and a background of DIPNECH. Post-operatively, she is clinically in remission.

Conclusion: DIPNECH is a rare disorder consisting of nodular proliferation of airway neuroendocrine cells and has rarely been associated with ectopic ACTH production, with only one case reported in the literature.