Median 10 years follow-up of patients with covert Cushing’s syndrome: a case series

Background Ectopic adrenocorticotropic hormone secretion syndrome occurs in 10% of all patients with adrenocorticotropic-hormone-dependent hypercortisolism. It is usually associated with overt malignancies or with occult and indolent tumors. This study aims to confirm the source of ectopic adrenocorticotropic hormone in four patients with ectopic Cushing’s syndrome over time. Case presentation A 38-year-old Iranian man with Cushing’s syndrome underwent bilateral adrenalectomy since the source of ectopic adrenocorticotropic hormone secretion was not localized and pituitary imaging was normal. A whole-body scan revealed a right-lung tumoral mass with mediastinal lymph node metastasis. The mass was assumed a lung carcinoid tumor with mediastinal adenopathy. Right-lung mid-zone lobectomy and mediastinal lymphadenectomy were done. In a 47-year-old Iranian man with Cushing’s syndrome, whole-body computed tomography scan revealed a pulmonary nodule in the posterior segment of the left lower lobe of the lung. The third case was a 25-year-old Iranian man who presented with symptoms and signs of Cushing’s syndrome. Pituitary magnetic resonance imaging revealed a microadenoma 5 × 9 mm. Whole-body scan showed abnormal focal somatostatin receptors analog avid lesion in the posterior aspect of inferior third of right lung, highly suggestive of ectopic adrenocorticotropic-hormone-producing tumor. The last case was a 43-year-old Iranian woman with Marfan syndrome with a history of mitral and aortic valve replacement and chronic dissection of the aorta, who presented with symptoms and signs of Cushing’s syndrome. She underwent bilateral adrenalectomy 1 year later owing to failure to locate ectopic adrenocorticotropic hormone syndrome. Whole-body scan showed abnormally increased radiotracer uptake in the midline of the skull base and posterior aspect of the middle zone of left hemithorax and bed of left lobe of thyroid. Conclusion The clinical spectrum of ectopic adrenocorticotropic hormone secretion syndrome is wide, and distinguishing Cushing’s disease from ectopic adrenocorticotropic hormone secretion syndrome is difficult. Initial failure to identify a tumor is common. Pulmonary carcinoid or occult source of ectopic adrenocorticotropic hormone secretion syndrome is usually the cause. In occult cases of ectopic adrenocorticotropic hormone in which the tumor cannot be localized, serial follow-up with serial computed tomography, magnetic resonance imaging, or scintigraphy is recommended for several years until the tumor can be localized and treated.

Use of 18F-FDG PET/CT to differentiate ectopic adrenocorticotropic hormone-secreting lung tumors from tumor-like pulmonary infections in patients with ectopic Cushing syndrome

Background: Ectopic adrenocorticotropic hormone (ACTH)-secreting lung tumors represent the most common cause of ectopic Cushing syndrome (ECS). Pulmonary opportunistic infections are associated with ECS and occasionally difficult to differentiate from tumors by using computed tomography (CT) alone. The present study aimed to evaluate the usefulness of 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT (18F-FDG PET/CT) for differentiating ectopic ACTH-secreting lung tumors from tumor-like pulmonary infections in patients with ECS.Methods: We retrospectively reviewed the imaging data for 24 patients with ECS who were suspected to have ACTH-secreting lung tumors and underwent 18F-FDG PET/CT between 2008 and 2019. Part of the 24 patients underwent 99mTc-HYNIC-TOC scintigraphy and 68Ga-DOTA-TATE PET/CT.Results: In total, 18 patients had lung tumors and six had pulmonary infections. The primary source of ECS remained occult in the six patients with pulmonary infections. The maximum standardized uptake value (SUVmax) for pulmonary infections was significantly higher than that for tumors (P = 0.008). Receiver operating characteristic analysis was performed, and it was found that a cut-off SUVmax of 4.95 helped in differentiating lung tumors from infections with 75% sensitivity and 94.4% specificity. In a subgroup analysis of 12 typical and five atypical carcinoids, there was no significant between-group difference with respect to SUVmax, the lesion size, the ACTH level, and the prevalence of regional lymph node metastasis. Four out of 6 patients with 5 infectious lesions and 16 out of 18 patients with 16 ACTH-secreting tumors underwent 99mTc-HYNIC-TOC scintigraphy, and 1/6 patients with 1 infectious lesion, and 6 out of 18 patients with 6 ACTH-secreting tumors underwent 68Ga-DOTA-TATE PET/CT. There is no significant difference in sensitivity between tumor lesions and infections using 99mTc-HYNIC-TOC scintigraphy. Conclusions: Our findings suggest that pulmonary infections exhibit significantly higher FDG uptake than do well-differentiated ACTH-secreting lung tumors in 18F-FDG PET/CT. Therefore, SUVmax (cut-off 4.95) may be useful for differentiating the two conditions. However, 99mTc-HYNIC-TOC scintigraphy is of no value in distinguishing the focus of well-differentiated ACTH-secreting lung tumors from that of infection. Typical and atypical ACTH-secreting lung carcinoids may show similar clinical behavior and appearance on 18F-FDG PET/CT.

Diagnosis and management of small pulmonary atypical carcinoid tumor associated with Cushing syndrome

Ectopic adrenocorticotropic hormone ( ACTH) syndrome is rare and identification of its source is often challenging. We report the case of an ectopic Cushing syndrome in a young adult male secondary to an occult ACTH producing atypical carcinoid tumor. Extensive biochemical and imaging workup was unrevealing. The diagnosis was aided by Ga-DOTA PET scan demonstrating a suspicious left upper lobe lung nodule. The patient underwent video-assisted thoracoscopic exploration with wedge resection and mediastinal lymphadenectomy of a T2aN2M0 atypical carcinoid, resulting in the normalization of ACTH levels and complete resolution of symptoms. The role of a Ga-DOTA PET scan in diagnosing pulmonary carcinoid tumors and their management are discussed.