[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) positron emission tomography imaging of thymic carcinoid tumor presenting with recurrent Cushing’s syndrome

Abstract

We report a case of a young woman with Cushing's syndrome (CS), in whom although endocrine investigations and negative pituitary imaging were suggestive of ectopic ACTH secretion, the results of inferior petrosal sinus (IPS) sampling after coricotropin-releasing hormone (CRH) stimulation were suggestive of pituitary ACTH hypersecretion.111 In-labelled octreotide and high-resolution computer tomography (CT) revealed a lesion possibly responsible for the ACTH source in the thymus. Thymectomy confirmed concomitant ectopic CRH and probable ACTH production by a thymic neuroendocrine carcinoma. After an 8-year remission period the patient developed a clinical and biochemical relapse. A high-resolution computed tomography (CT) scan of the thorax showed a 2-cm nodule in the thymic bed, which was positive on a [ Case reportA 25-year-old woman initially presented with recentonset depression, hirsuitism, acne and bruising suggestive of Cushing's syndrome (CS); clinical examination revealed arterial hypertension (170/120 mmHg) and mild proximal myopathy. Subsequent investigations showed hypokalemic alkalosis (serum K þ , 2.3 mmol/l (normal range 3.5 -5.0 mmol/l); HCO 3 , 32 mmol/l (normal levels 24^2 mmol/l)), marked hyperandrogenemia (testosterone, 12.5 nmol/l (normal range 0.5 -2.5 nmol/l)), normal fasting glucose concentrations and autonomous hypercortisolemia (elevated 24-h urinary free cortisol (UFC) of 4064 nmol per 24 h (normal range 20 -300 nmol per 24 h), serum midnight cortisol of 1161 nmol/l and inadequate cortisol suppression to a formal low-dose dexamethasone suppression test).An ectopic source of adrenocorticotropic hormone (ACTH) secretion was suggested by a marked elevated plasma ACTH concentration (1350 ng/l (normal values , 25 ng/l)), and a failure to suppress serum cortisol following a high-dose dexamethasone suppression test (HDDST). Inferior petrosal sinus (IPS) sampling after corticotropin-releasing hormone (CRH) stimulation, however, was more in keeping with Cushing's disease than with ectopic ACTH production as it showed a brisk ACTH increment following CRH administration (Table 1) (Fig. 1A). A further high-resolution CT showed a 2-cm thymic nodule in the upper mediastinum. Whole-body catheterization and sampling did not reveal an ectopic ACTH source. However, a greater than 3:1 CRH gradient suggestive of ectopic CRH production between the left brachiocephalic vein (BCV) and superior vena cava (SVC) and their simultaneous peripheral samples (BCV, 90 pg/ml and SVC, 100 pg/ml vs 30 pg/ml respectively) was shown. Based on the above findings a working diagnosis of a neuroendpcrine tumor of the thymus (thymic carcinoid tumor) secreting CRH was made.The patient underwent a mediastinotomy and thymectomy. A central firm nodule within the thymus

Evaluation of the diagnostic criteria for Cushing’s disease in Japan [Review]

“…The ability to detect pituitary ACTH-secreting adenoma might be improved by using a 3 Tesla magnet, although small non-functioning adenoma can also be detected with this technique. In some cases of EAS, 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) would be helpful in detecting the localization [32].…”

Paraneoplastic syndromes secondary to neuroendocrine tumours

“…In such cases, patients have high CRH levels in plasma and tumour tissue, whereas plasma ACTH levels are also increased; CS due to CRH production does not have a distinctive presentation, and endocrine testing may represent an interplay between ectopic and eutopic production (DeLellis & Xia 2003, Zangeneh et al 2003, Markou et al 2005. It has been suggested that no single endocrine test and/or imaging procedure are accurate enough to diagnose and localise ectopic ACTH/CRH-producing bronchial carcinoids, particularly as false positive IPSS results may occasionally be obtained, albeit very rarely (Young et al 1998, de Herder & Lamberts 1999, Baudin et al 2001, Loli et al 2003.…”

“…It has been suggested that no single endocrine test and/or imaging procedure are accurate enough to diagnose and localise ectopic ACTH/CRH-producing bronchial carcinoids, particularly as false positive IPSS results may occasionally be obtained, albeit very rarely (Young et al 1998, de Herder & Lamberts 1999, Baudin et al 2001, Loli et al 2003. In such cases, scintigraphy with 111 In-octreotide, particularly after correction of hypercortisolaemia, and PET using several novel tracers can be used to reveal confounding cases eluding localisation (de Herder et al 1994, Tsagarakis et al 2003, Kaltsas et al 2004b, Markou et al 2005. The recent finding that dopamine receptors are expressed in NETs associated with CS, and that the dopamine agonist cabergoline could be effective in controlling cortisol excess in a subgroup of such patients, provides further medical therapeutic options to control the hypercortisolism while awaiting definitive diagnosis , Pivonello et al 2007.…”

Evaluation of Diagnostic Tests for ACTH-Dependent Cushing’s Syndrome

“…The ability of MRI to detect pituitary ACTH-secreting adenomas in patients with Cushing's disease is, however, limited, because the calculated accuracy for detecting a pituitary source of ACTH is reported to be almost 60% for MRI [18]. In some cases of EAS, (18) F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) would be helpful to detect the localization [19]. Cavenous or inferior petrosal sinus sampling is also often used in the differential diagnosis of Cushing's syndrome [20].…”