Non Obvious Diagnosis of an Occult ACTH Dependent Cushing Syndrome

Autori

  • Adriano Naselli Endocrinology Unit, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania
  • Dario Tumino Endocrinology Unit, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania
  • Francesco Frasca Endocrinology Unit, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania

DOI:

https://doi.org/10.6092/1828-6550/APMB.106.2.2018.A2

Parole chiave:

Cushing, Ectopic, Covert, Occult

Abstract

A 54 years old man was admitted to our hospital due to progressive signs and symptoms of Cushing syndrome. Once a biochemical diagnosis of Adrenocorticotropic Hormone (ACTH)-dependent hypercortisolism was established, high dose 8 mg overnight Dexamethasone Suppression Test (HDDST), 1-deamino-8-D-arginine vasopressin (DDAVP) stimulation test and a Magnetic Resonance Imaging (MRI) led to conflicting results and an ectopic ACTH syndrome was diagnosed following a Bilateral Inferior Petrosal Sinus Sampling (BIPPS).
The localization of the source of ectopic ACTH secretion turned out to be a challenging task because most of imaging exams gave a negative result. After a prolonged follow-up, a chest Computed Tomography (CT) scan gave a morphological confirmation of a small focus in the right lung previously detected by a 68Gallium-DOTATOC- Positron Emission Tomography (PET). A right lower lobectomy of the lung was performed and an ACTH-positive typical pulmonary carcinoid was diagnosed. Before surgery, a good management of hypercortisolism was obtained with somatostatin analog lanreotide for years, and only after a likely escape phenomenon was successfully prescribedoff-labelpasireotide. In this patient with occult ectopic ACTH syndrome (EAS), a watchful waiting approach, based on imaging re-evaluation,representeda valuable option, provided that a good management of hypercortisolism and its end-organ complications wasobtained

Biografia autore

  • Dario Tumino, Endocrinology Unit, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania
    Endocrinology Unit, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Hospital, University of Catania, Catania

Riferimenti bibliografici

1. Nieman, L.K., Biller, B.M.K., Findling, J.W., Newell-Price, J., Savage, M.O., Stewart, P.M. et al. (2008). The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J ClinEndocrinolMetab. 93: 1526–1540. doi: 10.1210/jc.2008-0125.

2. Alexandraki, K.I., Grossman AB (2010). The ectopic ACTH syndrome. Rev EndocrMetabDisord. 11: 117–126. doi: 10.1007/s11154-010-9139-z.

3. Lacroix A, Feelders RA, Stratakis CA, Nieman LK (2015). Cushing's syndrome. Lancet. 386(9996):913-27. doi: 10.1016/S0140-6736(14)61375-1.

4. Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK (2005). Cushing’s syndrome due to ectopic corticotropin secretion: twenty years’ experience at the National Institutes of Health. J ClinEndocrinolMetab. 90: 4955–62. doi: 10.1210/jc.2004-2527.

5. Salgado LR, Fragoso MC, Knoepfelmacher M, Machado MC, Domenice S, Pereira MA, de Mendonça BB (2006). Ectopic ACTH syndrome: our experience with 25 cases. Eur J Endocrinol. 155(5):725-33. doi: 10.1530/eje.1.02278.

6. Isidori AM, Kaltsas GA, Pozza C, Frajese V, Newell-Price J, Reznek RH et al. (2006). The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and long-term follow-up. J ClinEndocrinolMetab. 91: 371–377. doi: 10.1210/jc.2005-1542.

7. Isidori AM, Sbardella E, Zatelli MC, Boschetti M, Vitale G, Colao A, Pivonello R; ABC Study Group. Conventional and Nuclear Medicine Imaging in Ectopic Cushing's Syndrome: A Systematic Review (2015). J ClinEndocrinolMetab. 100(9):3231-44. doi: 10.1210/JC.2015-1589.

8. Sundin A, Arnold R, Baudin E, Cwikla JB, Eriksson B, Fanti S, Fazio N, Giammarile F, Hicks RJ, Kjaer A, Krenning E, Kwekkeboom D, Lombard-Bohas C, O'Connor JM, O'Toole D, Rockall A, Wiedenmann B, Valle JW, Vullierme MP; Antibes Consensus Conference participants (2017). ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological, Nuclear Medicine & Hybrid Imaging. Neuroendocrinology. 105(3):212-244. doi: 10.1159/000471879.

9. Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO, Tabarin A; Endocrine Society. (2015). Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J ClinEndocrinolMetab. 100(8):2807-31. doi: 10.1210/jc.2015-1818.

10. Santhanam P, Taieb D, Giovanella L, Treglia G (2015). PET imaging in ectopic Cushing syndrome: a systematic review. Endocrine. 50(2):297-305. doi: 10.1007/s12020-015-0689-4.

11. Johnbeck CB, Knigge U, Kjær A (2014). PET tracers for somatostatin receptor imaging of neuroendocrine tumors: current status and review of the literature. Future Oncol. 10(14):2259-77.

12. Geijer H, Breimer LH (2013). Somatostatin receptor PET/CT in neuroendocrine tumours: update on systematic review and meta-analysis. Eur J NuclMedMolImaging. 40(11):1770-80. doi: 10.1007/s00259-013-2482-z.

13.Treglia G, Castaldi P, Rindi G, Giordano A, Rufini V (2012). Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis. Endocrine. 42(1):80-7. doi: 10.1007/s12020-012-9631-1.

14. Yang J, Kan Y, Ge BH, Yuan L, Li C, Zhao W (2014). Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis. ActaRadiol. 55(4):389-98. doi: 10.1177/0284185113496679.

15. De Bruin C, Hofland LJ, Nieman LK, van Koetsveld PM, Waaijers AM, Sprij-Mooij DM, van Essen M, Lamberts SW, de Herder WW, Feelders RA (2012). Mifepristone effects on tumor somatostatin receptor expression in two patients with Cushing's syndrome due to ectopic adrenocorticotropin secretion. J ClinEndocrinolMetab. 97(2):455-62. doi: 10.1210/jc.2011-1264.

16. Wolin EM, Jarzab B, Eriksson B, Walter T, Toumpanakis C, Morse MA, Tomassetti P, Weber MM, Fogelman DR, Ramage J, Poon D, Gadbaw B, Li J, Pasieka JL, Mahamat A, Swahn F, Newell-Price J, Mansoor W, Öberg K (2015). Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues. Drug Des DevelTher. 9:5075-86. doi: 10.2147/DDDT.S84177.

17. Öberg K, Lamberts SW (2016). Somatostatin analogues in acromegaly and gastroenteropancreatic neuroendocrine tumours: past, present and future. EndocrRelat Cancer. 23(12):R551-R566. doi: 10.1530/ERC-16-0151.

18. Kvols LK, Oberg KE, O'Dorisio TM, Mohideen P, de Herder WW, Arnold R, Hu K, Zhang Y, Hughes G, Anthony L, Wiedenmann B (2012). Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study. EndocrRelat Cancer. 19(5):657-66. doi: 10.1530/ERC-11-0367.

19. Clinical Trials.Gov "SOM 230 Ectopic ACTH-producing Tumors".

Dowloads

Pubblicato

2018-12-18

Fascicolo

V. 106 N. 2 (2018)

Sezione

CLINICAL CASE SEMINAR

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