Division of Endocrinology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA E-mail: runyu@mednet.ucla.edu إفراز هرمون القشرة الكظرية من ورم الكارسينويد الرئوي والذي مت تشخيصة بأستخدام التصوير املقطعي بواسطة لنظري املشع جاليوم68 ران يو Adrenocorticotropic Hormone-Secreting, Subcentimetre Lung Carcinoid Identified by 68Gallium-DOTATATE Positron Emission Tomography Scan Run Yu A 64-year-old male patient presented to the endocrine clinic at David Geffen School of Medicine, University of California, Los Angeles, USA, in 2018 with fatigue and weight gain for 1.5 years and bilateral thigh muscle pain and weakness for a few months. He also had hypertension and type-2 diabetes but no known osteoporosis. Physical examination noted Cushingoid features—such as truncal obesity and proximal amyotrophy; therefore, Cushing’s syndrome was suspected. He did not take cortico- steroids. Levels of 24-hour urinary free cortisol, mid- night salivary cortisol, morning cortisol levels after 1 mg dexamethasone and random morning adreno- corticotropic hormone (ACTH) were elevated over multiple measurements [Table 1]. Subsequently, the patient was diagnosed with ACTH-dependent Cushing’s syndrome. Pituitary magnetic resonance imaging (MRI) scans showed normal pituitary gland without evidence of Sultan Qaboos University Med J, May 2019, Vol. 19, Iss. 2, pp. e166–167, Epub. 8 Sep 19 Submitted 21 Oct 18 Revision Req. 23 Dec 18; Revision Recd. 3 Jan 19 Accepted 17 Jan 19 Figure 1: 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) with contrast scans of a 64-year-old male patient with ectopic Cushing’s syndrome showing the (A) coronal and (B) axial views of fused DOTATATE PET/CT and (C) coronal and (D) axial views of chest CT with an abnormal signal in the left upper lung nodule (arrows). This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License. https://doi.org/10.18295/squmj.2019.19.02.016 interesting medical image https://creativecommons.org/licenses/by-nd/4.0/ Run Yu Interesting Medical Image | e167 pituitary or suprasellar masses. Inferior petrosal sinus sampling demonstrated no lateralisation or central-to- peripheral ACTH gradient before or after corticotropin- releasing hormone administration, suggesting a peripheral source of ACTH secretion. Computed tomography (CT) scans of the neck, chest, abdomen and pelvis for a recent trauma did not identify clear tumours in the lungs, pancreas or other organs. 68Gallium(Ga)-DOTA- TATE positron emission tomography (PET)/CT scan with contrast showed a 9 × 6 mm, left upper lobe pulmonary nodule with a maximum standardised uptake value of 3 as the only abnormal finding [Figure 1]. The patient underwent left upper lung lobe wedge resection. At 8:00 a.m. on post-operative day 1, ACTH level was 2 pg/ml and cortisol 4 µg/dL; on post-operative day 2, at the same time, ACTH level was 7 pg/ml and cortisol 2 µg/dL, indicating complete remission of ACTH- dependent Cushing’s syndrome. Surgical histology revealed a low-grade neuroendocrine tumour which is a typical lung carcinoid without lymph node metastasis. Immunocytochemistry showed a positive expression of ACTH. The patient was treated with hydrocortisone with a plan of gradual dose tapering. He was followed- up for eight months post-operatively. All Cushingoid features, including hypertension and diabetes, disapp- eared after the tumour resection. Comment The current patient had elevated levels of 24-hour urine free cortisol and midnight saliva cortisol and unsuppressed levels of morning cortisol after taking dexamethasone. These findings are a clear indication of Cushing’s syndrome, which is defined as autonomous cortisol over-production.1 As his random morning ACTH levels were also elevated, his Cushing’s syndrome was ACTH-dependent.1 Although the vast majority of ACTH-dependent Cushing’s syndromes are caused by ACTH-secreting pituitary tumours, some are caused by ACTH-secreting tumours from other organs (e.g. ectopic Cushing’s syndrome), such as the lungs and pancreas.2 The normal pituitary gland of this patient revealed by an MRI scan suggested ectopic Cushing’s syndrome, which was confirmed by inferior petrosal sinus sampling.1,2 Locating an ectopic ACTH- secreting tumour can be challenging as it is often small and difficult to find by conventional imaging such as CT, MRI including diffusion weighted imaging, octreotide scan or fluorodeoxyglucose PET.3,4 68Ga-DOTATATE PET utilises a positron-emitting radioisotope-linked somatostatin analogue and has much higher spatial resolution and sensitivity than an octreotide scan in identifying neuroendocrine tumours, which comprise most ectopic ACTH-secreting tumours.2,5,6 As shown in the current case, 68Ga-DOTATATE PET is usually combined with contrast-enhanced CT and is the most sensitive imaging method in locating a covert ectopic ACTH-secreting tumour.3 References 1. Nieman LK. Diagnosis of Cushing's syndrome in the modern era. Endocrinol Metab Clin North Am 2018; 47:259−73. https://doi.org/10.1016/j.ecl.2018.02.001. 2. Alexandraki KI, Grossman AB. The ectopic ACTH syndrome. Rev Endocr Metab Disord 2010; 11:117−26. https://doi.org/10.1 007/s11154-010-9139-z. 3. Isidori AM, Sbardella E, Zatelli MC, Boschetti M, Vitale G, Colao A, et al. Conventional and nuclear medicine imaging in ectopic Cushing's syndrome: A systematic review. J Clin Endocrinol Metab 2015; 100:3231−44. https://doi.org/10.1210/ JC.2015-1589. 4. Razek AA. Diffusion magnetic resonance imaging of chest tumors. Cancer Imaging 2012; 12:452−63. https://doi.org/10.11 02/1470-7330.2012.0041. 5. Kunikowska J, Lewington V, Krolicki L. Optimizing somato- statin receptor imaging in patients with neuroendocrine tumors: The impact of 99mTc-HYNICTOC SPECT/SPECT/CT versus 68Ga-DOTATATE PET/CT upon clinical management. Clin Nucl Med 2017; 42:905−11. https://doi.org/10.1097/RLU.00000000 00001877. 6. Yu R, Wachsman A. Imaging of neuroendocrine tumors: Indi- cations, interpretations, limits, and pitfalls. Endocrinol Metab Clin North Am 2017; 46:795−814. https://doi.org/10.1016/j. ecl.2017.04.008. Table 1: Laboratory investigations of a 64-year-old male patient with ectopic Cushing’s syndrome Investigation Measurement one Measurement two Measurement three Measurement four Normal range 24-hour urinary free cortisol levels in µg/day 95.5 198.1 202.9 221.7 ≤60 Midnight salivary cortisol levels in µg/dL 0.430 0.736 0.929 - <0.112 Morning cortisol levels after 1 mg dexamethasone in µg/dL 14 19 - - <1.8 Random morning ACTH levels in pg/mL 70 98 99 - 6–59 ACTH = adrenocorticotropic hormone. https://doi.org/10.1016/j.ecl.2018.02.001 https://doi.org/10.1007/s11154-010-9139-z https://doi.org/10.1007/s11154-010-9139-z https://doi.org/10.1210/JC.2015-1589 https://doi.org/10.1210/JC.2015-1589 https://doi.org/10.1102/1470-7330.2012.0041 https://doi.org/10.1102/1470-7330.2012.0041 https://doi.org/10.1097/RLU.0000000000001877 https://doi.org/10.1097/RLU.0000000000001877 https://doi.org/10.1016/j.ecl.2017.04.008 https://doi.org/10.1016/j.ecl.2017.04.008