SFEBES2023 Poster Presentations Adrenal and Cardiovascular (78 abstracts)
A clinical case demonstrating the challenges in diagnosing and managing Paraneoplastic Cushing’s Syndrome
Zohaib Iqbal 1 , Jan Ho 1 , Leanne Walker 2 , Ann White 2 , Philip Monaghan 1 , Sally Thirkettle 1 , Aziz Gulamhusein 1 , Brian Keevil 3 , Wasat Mansoor 1 & Safwaan Adam 1
1The Christie Hospital, Manchester, United Kingdom. 2University of Manchester, Manchester, United Kingdom. 3Manchester Foundation Trust, Manchester, United Kingdom
We present a case of a 62-year-old lady with a grade 3 well-differentiated metastatic gastric-neuroendocrine tumour complicated by symptoms of CS (weight-gain, bruising, proximal weakness) which developed over 4 weeks. She had progressive disease after exhausting all conventional anti-neoplastic therapeutic options. Screening tests revealed raised 24-h urinary free cortisol (3460 nmol/24h[<165]), post-overnight dexamethasone suppression serum cortisol (serF) 1200 nmol/l(<50) (measured by immunoassay), mean (of 5) cortisol day curve (CDC) serF (CDC-serF) 1300 nmol/l but adrenocorticotropic hormone (ACTH) was in the normal range at 21 ng/l (0-46). Cross-sectional imaging of her pituitary and adrenal glands were unremarkable apart from bilaterally enlarged adrenals. ACTH precursors (pro-ACTH, proopiomelanocortin) were elevated: 3168 pmol/l (0-40). The patient commenced metyrapone, but intolerable nausea (at low doses with no evidence of hypocortisolaemia) precluded its use. Ketoconazole was contraindicated due to elevated transaminases therefore funding for the novel 11-β-hydroxylase inhibitor, osilodrostat, was obtained. Weekly CDC (serF measured by both immunoassay and liquid-chromatography tandem mass spectrometry [LC-MS/MS]) were undertaken for each dose escalation to assess the adequacy of treatment (target CDC-serF 120-240 nmol/l). Before starting osilodrostat, her CDC-serF was 1305 nmol/l. Following dose titration to 2 mg bd, her clinical symptoms of CS improved as did CDC-serF (to 115.8 nmol/l); replacement hydrocortisone was introduced. Bland-Altman revealed a 31% positive bias in serF measured by immunoassay compared to LC-MS/MS. This case highlights the utility of measuring ACTH precursors to prevent diagnostic delay. While ACTH precursors cross-react approximately 2% in most ACTH assays, if tumours primarily secrete POMC, the cross-reactivity can be lower and lead to ACTH concentrations in the normal range. We also demonstrate that LC-MS/MS should be used in osilodrostat-treated patients to measure serF due to the bias conferred by the build-up of cortisol precursors.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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