Cushing’s syndrome due to adrenocorticotropic hormone-secreting metastatic neuroendocrine tumor of unknown primary origin: a case report and literature review

Abstract

Background In this article, we present a case of neuroendocrine neoplasm of unknown primary origin (UPO NEN), which is a rare cause of ectopic Cushing's syndrome (ECS) presenting numerous challenges, together with a literature review. Case report A 43-year-old male patient presented with clinical features consistent with Cushing's syndrome (CS) and adrenocorticotropic hormone (ACTH)-dependent hypercortisolemia. Despite a suspicious lesion on pituitary MRI, the high-dose dexamethasone suppression test and bilateral inferior petrosal sinus sampling results were not compatible with Cushing's disease. Bilateral non-homogeneous opacities were observed in the thorax CT of the patient, who also had a history of COVID-19 infection, but no tumoral lesion was detected. When 68 Ga-SSTR PET/CT and 18 FDG-PET/CT were performed, multiple metastatic foci were detected in mediastinal and hilar lymph nodes and the axial skeleton. Paratrachealsubcarinal lymph nodes were excised mediastinoscopically, and the diagnosis of NEN was made. Histopathological findings indicated that the possible origin was an atypical pulmonary carcinoid with a low Ki-67 labeling index. After controlling hypercortisolemia, a regimen of somatostatin analogs and capecitabine plus temozolomide was decided upon as treatment by a multidisciplinary council. Conclusion This is a challenging case of UPO NEN presenting with ECS and confounding factors, such as previous infection and incidental lesions, during the diagnosis process. The case in question highlighted the fact that atypical pulmonary carcinoid with a low proliferation index may cause visible metastases even when radiologically undetectable.

Curcumin analogues exert potent inhibition on human and rat gonadal 3β-hydroxysteroid dehydrogenases as potential therapeutic agents: structure-activity relationship and in silico docking

“…Cushing’s syndrome (hypercorticism) is characterised with massive cortisol secretion, which may be because h 3β-HSD2 and r 3β-HSD1 in adrenal glands were upregulated 36 , 37 . Cushing’s syndrome is accompanied with obesity, hypertension, osteoporosis, and type II diabetes 38 , 39 and women’s PCOS is also a metabolic disease, which is characterised by excessive androgen secretion (hyperandrogenism), accompanied by insulin resistance, and polycystic ovary due to increased expression of 3β-HSD2 40 . Although trilostane is a moderate 3β-HSD2 inhibitor and was once used to treat Cushing’s syndrome 41 .…”

Ectopic Cushing's syndrome in a patient with metastatic Merkel cell carcinoma: A case report

“…Small cell lung carcinoma is a known cause of ECS, but in our patient imaging studies did not reveal any lung lesions. Recently, a case of metastatic NET of unknown origin presenting with ECS was reported[ 8 ]. Several manifestations of MCC-associated paraneoplastic syndromes have been reported[ 9 ], but ECS associated with MCC has not be described, even though a case of metastatic MCC within a cortisol-producing adrenal adenoma has been recently reported[ 10 ].…”

Exploring the Relationship between Obesity, Metabolic Syndrome and Neuroendocrine Neoplasms

“…In certain instances, weight gain can also be a biological consequence of functional NENs rather than a risk factor for tumor initiation. Firstly, the ectopic secretion of adrenocorticotropic hormone (ACTH) from pulmonary NETs has been described, resulting in Cushing's syndrome and unintentional weight gain [72][73][74]. In one case series of 918 GEP-NETs and thoracic NETs, the prevalence of ectopic ACTH secretion was reported to be 3.2% and associated with poorer patient survival [75].…”

“…In one case series of 918 GEP-NETs and thoracic NETs, the prevalence of ectopic ACTH secretion was reported to be 3.2% and associated with poorer patient survival [75]. In these cases, definitive therapy such as surgical resection can result in weight loss, although specific therapy for hypercortisolemia such as Metyrapone can also be used [72,74]. Secondly, insulinomas are rare tumors that may occur sporadically or in association with multiple endocrine neoplasia type 1 (MEN1) syndrome, and they can also manifest with weight gain as patients attempt to relieve hypoglycemic symptoms by excess food intake [76][77][78].…”