Diffuse Idiopathic Pulmonary Neuroendocrine cell hyperplasia (DIPNECH): an unusual case of cyclical ectopic adrenocorticotrophic hormone secretion


SN Ali, M Moriarty, L Yang Jon Anderson and JF Todd, Hammersmith Hospital


Case: A 33yr lady presented to her GP in June 2015 with weight gain, abdominal striae, proximal myopathy and secondary amenorrhoea. Clinically, she had features of Cushing’s syndrome. She had a previous Hx of asthma, but had stopped all inhalers/medications several months prior to presentation. A random cortisol performed by the GP was 4000nmol/L She was referred to her local DGH, and performed a normal 24 hour urinary cortisol collection, however failed to suppress on a Low Dose Dexamethasone Suppression Test (LDDST): T=48hr cortisol 409nmol/L and ACTH 35.2ng/L. A subsequent MRI pituitary scan showed a 5.5mm non-enhancing left-sided pituitary adenoma. She was then referred to Hammersmith Hospital (HH) for further management. Of note, she had had a previous episode of weight gain, abdominal striae, proximal myopathy and secondary amenorrhoea one year earlier which had subsided spontaneously after a few weeks.


When she was seen at Hammersmith Endocrine OP clinic, repeat investigations revealed a raised random cortisol (1,170nmol/L), raised ACTH (98.3ng/L), normal 24 hour urinary cortisol collection and confirmed failure to suppress cortisol levels on a LDDST with high ACTH levels (T=48hr cortisol 727nmol/L, ACTH 129ng/L). Cortisol Day curve showed high cortisol levels with no diurnal variation. An IPSS was performed, which failed to show a central to peripheral ACTH gradient. Therefore, this was unlikely to represent pituitary-driven Cushing’s disease. An ectopic source of ACTH was sought. A CT thorax/abdomen/pelvis showed multiple small pulmonary nodules with a dominant right lower lobe nodule persistent since a CT KUB in 2006 with some progression locally. The adrenal glands were entirely normal. Review in the lung MDT confirmed that these lung nodules were larger, more spiculated and unlikely to represent infection/TB. Gallium68 Dototate PET CT scan was showed no abnormal uptake. .She was commenced on oral Metyrapone, with the dose titrated up to 250mg tds to normalise cortisol levels. One week later, Metyrapone had to be reduced and then eventually stopped as cortisol levels came down dramatically. Off Metyrapone and on no treatment, cortisol levels remain low (116 to 209nmol/L) with concomitant reduction  ACTH levels (12-20ng/l,) indicating she had once again had spontaneous remission of Cushing’s syndrome. An excision biopsy of the right lung nodule was performed. Histology revealed  tumourlets with a typical carcinoid on a background of diffuse neuroendocrine hyperplasia (DIPNECH)  with focal positive staining for ACTH.


Conclusion: This case represents cyclical ectopic ACTH secretion caused by Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, DIPNECH; a rare disorder consisting of nodular proliferation of airway neuroendocrine cells. DIPNECH has rarely been associated with ectopic ACTH production, with only two cases reported in the literature. This is our second case of ectopic ACTH production caused by DIPNECH leading to cyclical Cushing’s Syndrome.