ESPE Abstracts

Background: Ectopic ACTH-producing tumors rarely occur in children, with <1% of all adolescents with Cushing Syndrome (CS). Many cases of ACTH-secreting ectopic neuroendocrine tumors (NETs) are reported in literature. In most patients, tumors secrete corticotropin-like peptides and/or corticotropin releasing factor (CRF)-like peptide, which stimulate cortisol hyperproduction.

Background: Ectopic ACTH-producing tumors rarely occur in children, with <1% of all adolescents with Cushing Syndrome (CS). Many cases of ACTH-secreting ectopic neuroendocrine tumors (NETs) are reported in literature. In most patients, tumors secrete corticotropin-like peptides and/or corticotropin releasing factor (CRF)-like peptide, which stimulate cortisol hyperproduction.

Case report: A 17-year-old girl presented to our hospital with a history of psychosis, progressive weight loss, recent onset widespread acne, hirsutism, amenorrhea and muscle weakness. Her height was 164 cm (+0.17 SDS), weight 43.6 Kg (-1.81 SDS) and body mass index (BMI) SDS was -2.31. At the physical examination we observed facial plethora and fullness, lower limb edema, “buffalo hump”, mild hirsutism and hypertension (BP 140/100 mmHg, > 99° pct). Blood tests showed fasting hyperglycemia (180 mg/dl) with HbA1c 49 mmol/mol and high levels of ACTH and plasma cortisol according to circadian rhythm (at 00.00 am: ACTH 34,1 pg/ml, range 0–42, cortisol 63,84 mcg/ml, range 4–22, at 8.00 a.m.: ACTH: 62,7 pg/ml—cortisol: 84,96 mcg/dl). We performed overnight 1 mg and a high-dose suppression test with 8 mg of dexamethasone, without suppression of adrenal axis (at 8 am: ACTH 179 pg/ml, cortisol 69 mcg/dl). High levels of free urinary cortisol were detected in a 24-h urine collection (>510 mcg/24 h). Moreover, hypokaliemia (K 2.4 mEq/L) and mild anaemia (Hb 9.2 g/dl) were found. Negative NET markers were observed. Ultrasonography and abdominal magnetic resonance imaging (MRI) showed bilateral adrenal gland hyperplasia. Brain MRI showed normal pituitary gland. Total body CT was negative for tumor lesions but vertebral fractures and aseptic necrosis of the femoral head was identified. Pharmacological treatment of hypercortisolism was started using metyrapone therapy 1000 mg/day. After one week of therapy we found normal ACTH and cortisol levels. Gallium-68 labelled somatostatin receptor and FDG PET/CT was performed in order to identify paraneoplastic NET lesion. A small lesion (1.4 cm) was found in thymus. Transthoracic surgery was performed, and pathological examination revealed atypical thymic carcinoid. After surgery, ACTH and cortisol levels were normal, 34 pg/ml and 16.25 ng/dl respectively.

Conclusion: EAS is a rare, often severe condition. Its management for diagnosis and treatment is considered a hard challenge for paediatric endocrinologists. In the future, advances in imaging techniques will improve the identification of small occult NETs and thus allow their removal.