A 41-year-old woman presented with a puffy face since five months. She experienced alopecia, hirsutism, easy bruisability, amenorrhea and proximal muscle weakness. Clinical examination revealed a moonface, centripetal obesity, proximal muscle atrophy, thinned scalp hair, hyperpigmentation in sun-exposed neck region, ecchymosis and arterial hypertension grade 1. Blood analysis showed elevated morning cortisol, elevated morning ACTH of 66.1 pg/ml (normal 1060), hypokalemic metabolic alkalosis (potassium 2.6 mmol/l, bicarbonate 34 mmol/l) and hypernatremia (149 mmol/l). Cushings syndrome was diagnosed with elevated 24-hours urinary cortisol excretion of 963 μg/24 hours (normal 21292) and elevated late-night salivary cortisol of 0.437 μg/dl (normal <0.107). Loss of circadian rhythm and high ACTH and cortisol values at midnight confirmed ACTH dependency. No adenoma could be visualised on MRI of the pituitary gland. Inferior petrosal sinus sampling (IPSS) displayed a central-to-peripheral ACTH gradient of 2.8: clearly above the cut-off of 2.0. Surprisingly, we did not observe the expected rise in ACTH gradient after CRH-stimulation, with a gradient below 3.0 (1.4 after 5 min and 1.2 after 10 min). Additional PET-CT showed intense metabolic activity in the left anterior ethmoidal sinus and left upper nasal turbinate, extending to the middle and lower left nasal cavity. Biopsy of this polypoid lesion revealed an olfactory neuroblastoma (ONB) with positive immunostaining for ACTH. Our patient underwent endoscopic resection of the tumour as far as the lamina cribrosa, including resection of the entire middle turbinate. The exposed dura mater and the nasal septum showed no signs of tumour invasion. Postoperative values of cortisol and ACTH were undetectable, suggestive for successful resection. Anatomopathological analysis confirmed our previous diagnosis. Olfactory neuroblastoma (syn. esthesioneuroblastoma) is a rare neoplasm originating from neuroectodermal olfactory cells situated in the upper nasal cavity, representing about 3% of all sinonasal malignancies. ONB presenting with ectopic ACTH syndrome (EAS) is extremely rare. To our knowledge, only 18 cases have been published. Clinicians should be aware that inconsistent IPSS results might be due to an ACTH-producing tumour in the sinonasal region, which can be explained by the anatomical proximity to the venous drainage of the pituitary gland. In case of EAS, especially with inconsistent IPSS results, one should always follow ones nose and look at the sinonasal region.
Keywords: Cushings syndrome, ectopic ACTH syndrome, esthesioneuroblastoma, olfactory neuroblastoma, IPSS
18 - 21 May 2019
European Society of Endocrinology