Abstract
A 51-year old woman was admitted with multiple cerebral, pulmonary and intra-abdominal abscesses. The combination of apparent immunosuppression, obesity, diabetes mellitus, hypertension, hypokalaemia, osteoporotic fractures and bilateral shoulder avascular necrosis led to a clinical diagnosis of Cushing’s syndrome (CS). This was biochemically confirmed as follows: midnight serum Cortisol 4275 nmol/L (60–250), non-suppressed overnight dexamethasone suppression test, raised salivary Cortisol 716 nmol/L (5–46) and ACTH 639 ng/L (0–46). Urinary free Cortisol was elevated >75,000 nmol/L (<165). Urinary steroid metabolites measured by Gas Chromatography Mass Spectrometry were markedly increased: tetrahydrocortisol (THF) 219024 µg/24h and tetrahydrocortisone (THE) 88848 µg/24h. The (THF+5αTHF)/THE ratio was 2.8 (≤1). Pituitary MRI was unremarkable and whole body CT scanning showed a thymic tumour and bilateral adrenal hyperplasia. Urinary 5HIAA was marginally raised with a normal chromogranin A. She underwent a thymectomy which confirmed a ‘paraganglioid’ variant of a thymic carcinoid tumour. We describe a case of ACTH-secreting thymic carcinoid that presented with florid clinical and biochemical features of CS, but no carcinoid syndrome. The (THF+5αTHF)/THE ratio is reported to be a useful indicator in differentiating the aetiologies of CS, although this was not the case in our patient. In this article we examine the degree to which the various urinary steroid metabolites were raised in this patient with florid CS and compare them with some normative data obtained from patients with either Cushing’s disease or the normal population. We hereby postulate that steroid metabolomics profiling may be helpful in establishing the differential diagnosis of CS.
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Hauso O, Gustafsson BI, Kidd M, et al, 2008 Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer 113: 2655–2664.
Modlin IM, Oberg K, Chung DC, et al, 2008 Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 9: 61–72.
Barakat MT, Meeran K, Bloom SR, 2004 Neuroendocrine tumours. Endocr Relat Cancer 11: 1–18.
Bi Y, Liu R, Ye L, et al, 2009. Gene expression profiles of thymic neuroendocrine tumors (carcinoids) with ectopic ACTH syndrome reveal novel molecular mechanism. Endocr Relat Cancer 16: 1273–1282.
Öberg K, Hellman P, Ferolla P, 2012 Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23: 120–123.
Duh QY, Hybarger CP, Geist R, et al, 1987 Carcinoids associated with multiple endocrine neoplasia syndromes. Am J Surg 154: 142–148.
Kondo K, Monden Y, 2003 Lymphogenous and hematogenous metastasis of thymic epithelial tumors. Ann Thorac Surg 76: 1859–1864.
Arlt W, Biehl M, Taylor AE, et al, 2011 Urine steroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumors. J Clin Endocrinol Metab 96: 3775–3784.
Chortis V, Bancos I, Sitch AJ, et al, 2016 Urine steroid metabolomics is a highly sensitive tool for post-operative recurrence detection in adrenocortical carcinoma. European conference of endocrinology. Endocrine abstracts. https://doi.org/www.endocrine-abstracts.org/ea/0041/ea0041OC1.4.htm.
Lang K, Beuschlein F, Biehl M, et al, 2015 Urine steroid metabolomics as a diagnostic tool in primary aldosteronism. Endocrine abstracts. https://doi.org/www.endocrine-abstracts.org/ea/0038/ea0038oc1.6.htm
Jansson JO, Svensson J, Bengtsson BA, et al, 1998 Acromegaly and Cushing’s syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6. Clin Endocrinol 48: 243–250.
Laat JM de, Pieterman CR, van den Broek MF, et al, 2014 Natural Course and Survival of Neuroendocrine Tumors of Thymus and Lung in MEN1 Patients. J Clin Endocrinol Metab 99: 3325–3333.
Neary NM, Lopez-Chavez A, Abel BS, et al, 2012 Neuroendocrine ACTH-producing tumor of the thymus—experience with 12 patients over 25 years. J Clin Endocrinol Metab 97: 2223–2230.
Stewart PM, Walker BR, Holder G, et al, 1995 11 beta-Hydroxysteroid dehydrogenase activity in Cushing’s syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 80: 3617–3620.
Wolthers BG, Kraan GP, 1999 Clinical applications of gas chromatography and gas chromatography-mass spectrometry of steroids. J Chromatogr A 843: 247–274.
Palermo M, Shackleton CH, Mantero F, et al, 1996 Urinary free cortisone and the assessment of 11 beta-hydroxysteroid dehydrogenase activity in man. Clin Endocrinol 45: 605–611.
Fong BM-W, Tam S, Leung KS-Y, 2010. Improved liquid chromatography-tandem mass spectrometry method in clinical utility for the diagnosis of Cushing’s syndrome. Anal Bioanal Chem 396: 783–790.
Stiefel P, García-Morillo JS, Jimenez L, et al, 2002 Role of ketoconazole treatment in urinary-free cortisol-to-cortisone and tetrahydrocortisol-to-tetrahydrocortisone ratios in nonectopic Cushing’s syndrome. Endocrine 18: 279–284.
Turpeinen U, Markkanen H, Sane T, et al, 2006 Determination of free tetrahydrocortisol and tetrahydrocortisone ratio in urine by liquid chromatography-tandem mass spectrometry. Scand J Clin Lab Invest 66: 147–159.
Brossaud J, Ducint D, Corcuff J-B, 2016 Urinary glucocorticoid metabolites: biomarkers to classify adrenal incidentalomas? Clin Endocrinol 84: 236–243.
Valeriani M, Agolli L, Falco T, et al, 2012 A case report of metastatic atypical thymic carcinoid with ectopic ACTH production: locoregional control after adaptive radiation treatment. Tumori 98: 172–175.
Modlin IM, Sandor A, 1997 An analysis of 8305 cases of carcinoid tumors. Cancer 79: 813–829.
McEvoy MP, Rich BS, New M, et al, 2011 Thymic carcinoid presenting with Cushing’s syndrome in a 17-year-old boy: a case report and review of the literature. J Clin Oncol 29: 716–718.
Isidori AM, Kaltsas GA, Pozza C, et al, 2006 The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and long-term follow-up. J Clin Endocrinol Metab 91: 371–377.
Page-Wilson G, Freda PU, Jacobs TP, et al, 2014 Clinical Utility of Plasma POMC and AgRP Measurements in the Differential Diagnosis of ACTH-Dependent Cushing’s Syndrome. J Clin Endocrinol Metab 99: 1838–1845.
Monaghan PJ, Kyriacou A, Sturgeon C, et al, 2016 Proopiomelanocortin interference in the measurement of adrenocorticotrophic hormone: a United Kingdom National External Quality Assessment Service study. Clin Endocrinol (Oxf) 85: 569–574.
Ilias I, Torpy DJ, Pacak K, et al, 2005 Cushing’s syndrome due to ectopic corticotropin secretion: twenty years’ experience at the National Institutes of Health. J Clin Endocrinol Metab 90: 4955–4962.
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Kyriacou, A., Stepien, K.M. & Issa, B. Urinary steroid metabolites in a case of florid Ectopic Cushing’s syndrome and clinical correlations. Hormones 15, 540–547 (2016). https://doi.org/10.14310/horm.2002.1695
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DOI: https://doi.org/10.14310/horm.2002.1695