A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing’s syndrome

Abstract

SummaryWe present a case of a young female patient with a rare cause of relapsing and remitting Cushing’s syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing’s syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms ‘relapsing and remitting’ in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing’s syndrome with thymic neuroendocrine tumours (NETs), although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking.Learning pointsEctopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing’s syndromeThere is a small but growing body of literature describing the correlation between ectopic ACTH secretion and thymic neuroendocrine tumours (NETs)The possibility of a MEN-1 syndrome should be considered in all patients with thymic NETs, and we note the observational association with male gender and cigarette smoking in this cohortAn exception to these associations is the finding of relatively high incidence of thymic NETs among female non-smoking MEN-1 patients in the Japanese compared with Western populationsThe relapsing and remitting course of our patient’s symptoms is noteworthy, given the paucity of this finding among other published cases

MANAGEMENT OF ENDOCRINE DISEASE: Cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion

“…Various symptoms including depressive symptoms are very frequent in Cushing's syndrome, but intense hypercortisolism may also result in steroid psychosis. The clinical picture often associates agitation or paranoid symptoms, with or without delusional episodes (129,130,131,132,133). True melancholic syndromes, refractory to standard therapy, may also occur.…”

“…It is based on a 24-h urinary free cortisol assay and/or measurement of cortisol and ACTH concentrations in several samples drawn during the day and at midnight. Aside from exceptional cases of cyclic EAS (12,133) , urinary free cortisol, serum cortisol and ACTH concentrations are usually dramatically increased (13,96), and are associated with loss of circadian rhythm (4,5,6,7,8,9,10,11,12,13,14). However, it should be mentioned that, in a life-threatening condition justifying an urgent initiation of specific treatments of hypercortisolism, the biochemical investigation should be reduced to a minimal evaluation including only one or two blood samples for cortisol and ACTH measurements.…”

Thymic Neuroendocrine Neoplasms: Biological Behaviour and Therapy

“…Thymic carcinoids with CS show a worse outcome than those without CS [38] , but it is unclear as to whether they are inherently more aggressive or that it is the metabolic complication of the CS which is responsible. The EAS may also be highly periodic, as reported in one Japanese patient [39] .…”

Paraneoplastic endocrine syndromes

“…Six recurrent patients developed metastatic disease and died 57 months following initial thymectomy (Neary et al 2012). Figure 1 illustrates a thymic carcinoid tumour which secreted ACTH intermittently to cause periodic Cushing's syndrome (Trott et al 2016).…”