Role of 68Ga-DOTATOC Positron Emission Tomography in Locating Pulmonary Neuroendocrine Tumor Presenting with ACTH-Dependent Cushing's Syndrome: A Case Report

Abstract

Background: In ectopic adrenocorticotropic hormone (ACTH) syndrome, locating the responsible lesion is often challenging. Case Presentation: A 68-year-old woman was transferred to Nara Medical University hospital for a detailed investigation of her ACTH-dependent Cushing's syndrome. Because of hypercortisolism-induced immunosuppression, she subsequently developed severe Nocardia pneumonia and was forced to temporarily depend on noninvasive positive pressure ventilation (NIPPV). Intravenous antifungal agents and antibiotics were administered, resulting in significant symptomatic improvement. Metyrapone was administered to suppress excessive cortisol. Contrast-enhanced magnetic resonance imaging of the pituitary revealed a 4 mm sized poorly enhanced area, and microadenoma was suspected. Although cavernous venous sampling was indispensable prior to trans-spheroidal surgery (TSS), this examination could not be performed because of the presence of deep vein thrombosis. TSS was performed for both diagnostic and therapeutic purposes, but hypercortisolism did not improve. Moreover, immunohistochemical findings of the specimen revealed nonfunctional pituitary tumor. Methods: We re-evaluated the responsible lesion causing ACTH-dependent Cushing's syndrome. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) revealed weak and abnormal FDG uptake in the right pericardium, but the possibility of nonspecific uptake could not be ruled out. However, gallium-68 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic-acid-D-Phe¹-Tyr³-octreotide (⁶⁸Ga-DOTATOC)-PET demonstrated the same degree of abnormal uptake; therefore, a functional pulmonary tumor was strongly suspected. Results: Video-Assisted Thoracic Surgery (VATS) was performed, and histopathological findings of the specimen revealed a neuroendocrine tumor with positive ACTH staining. After VATS, ACTH and cortisol levels were normalized. Conclusions: Here, we report a case of ACTH-dependent Cushing's syndrome caused by a lung neuroendocrine tumor, in which ⁶⁸Ga-DOTATOC PET was helpful in detecting the functional tumors.

Keywords: 68Ga-DOTATOC-PET; ACTH-dependent Cushing’s syndrome; neuroendocrine tumor.

Figure 1

Computed tomography (CT) of the chest demonstrating infiltrative shadow at the left upper lobe, suggesting fungal infection.

Figure 2

T1 gadolinium-enhanced magnetic resonance imaging (MRI) of the pituitary, revealing a 4 mm sized mass at the left anterior pituitary lobe (yellow arrow), suggesting pituitary adenoma.

Figure 3

Chest computed tomography (CT) after hospitalization showing aggravated infiltrative shadow accompanied by cavity formation, diagnosed as acute exacerbation of fungal pneumonia.

Figure 4

Multidisciplinary therapy was administered, including artificial respiration, antibiotics, antifungal agents, and systemic steroid pulse therapy. Various colors were used to clearly illustrate the types of antibiotics and their duration of use. Blue arrows indicated steroid pulse therapy using 1 gram per day of methylprednisolone. Red arrow and dashed line indicated the period during which NIPPV was performed. NIPPV: noninvasive positive pressure ventilation; ST: Sulfamethoxazole/Trimethoprim; LVFX: Levofloxacin; AMK: amikacin; VCM: Vancomycin; IPM/CS: Imipenem/Cilastatin; VRCZ: Voriconazole; AMPH-B: Amphotericin B; MCFG: Micafungin; MINO: minomycin; mPSL: methylprednisolone.

Figure 5

Metyrapone was administered to suppress excessive cortisol. The daily dose was started at 750 mg and gradually increased up to 2250 mg. Transsphenoidal surgery (TSS) was performed on 24 September; however, ACTH and cortisol levels remained unchanged. The vertical axis denotes ACTH and cortisol levels. The horizontal axis denotes time. 7/14: 14 July. The black and gray line graphs indicate serum cortisol and plasma ACTH levels, respectively.

Figure 6

Ectopic ACTH syndrome was controlled in combination with metyrapone and hydrocortisone. In due clinical course, ACTH and cortisol levels gradually decreased, suggesting cyclic Cushing’s syndrome. Right middle lobectomy was performed on 10 April. The vertical axis denotes ACTH and cortisol levels. The horizontal axis is for time. 10/6: 6 October. The black and gray line graphs indicate serum cortisol and plasma ACTH levels, respectively.

Figure 7

FDG-PET revealed 11 mm sized weak uptake (SUV max: 2.4) at the right pulmonary nodule (yellow allow) in contact with pericardium. The red crosshair was for calculating SUV max (A). Gallium-68 DOTATOC PET revealed abnormal uptake (SUV max: 4.1) at a similar lesion (yellow allow) where FDG was incorporated (B). This strongly suggested that this nodule was the lesion responsible for ectopic ACTH syndrome.

Figure 8

Immunohistochemically, the resected specimen revealed that the tumor was positive for synaptophysin, chromogranin A, CD56, and ACTH. The final diagnosis was ACTH-producing neuroendocrine tumor. The Ki-67-labeling index of the tumor cells was 2.7%.