Endocrine Abstracts

Background: Neuroendocrine tumours (NETs) are extremely rare in children and adolescents (incidence approximately 2.8 cases per million). Around 10-20% of paediatric NETs present with metastatic disease at diagnosis.

Aim: We present a case of metastatic poorly differentiated NET in a teenager with a suspected right lung primary as a rare cause of ACTH-dependent ectopic Cushing’s syndrome (CS).

Case presentation: A 15-year-old self-identified as male presented with non-specific symptoms of malaise and anxiety followed by generalised lymphadenopathy and rapid weight gain. On examination, he had a palpable abdominal mass, hypertension (150/101mmHg) and hyperglycaemia.

Investigations: Revealed elevated ACTH (143 ng/l), serum cortisol level (1516nmol/), urine cortisol (927nmol), hypokalaemia and hypophosphatemia. Whole-body imaging revealed a metastatic tumour (right adrenal, liver, pulmonary and pleura, bones and pelvis). Histopathology showed a high-grade, poorly differentiated carcinoma with a high KI-67 of 50%.

Management: A multidisciplinary team approach was engaged. Hypertension and steroid-induced hyperglycaemia were managed as per local guidelines. Given the neoplasm’s metastatic and poorly differentiated nature, he was started on carboplatin and etoposide chemotherapy and on Metyrapone, a potent inhibitor of the enzyme 11β-hydroxylase, which is crucial in cortisol biosynthesis. Metyrapone doses were titrated based on fortnightly and later monthly 24-hour cortisol profiles, aiming for cortisol levels of 300- 500 nmol/l. Maintenance hydrocortisone was added 48- hours after commencing Metyrapone to prevent adrenal crisis. Ten days after commencing Metyrapone, antihypertensives and insulin were discontinued. Denosumab was used for the metastatic bone lesions, and he was started on thromboprophylaxis, given the hypercoagulable nature of the disease. Ketoconazole was added 4 months later, however it was not well tolerated, so discontinued. Clinical symptoms improved, but there was no significant impact on tumour burden.

Discussion: Ectopic ACTH secretion is a very rare cause of CS in children and teenagers. Non-specific early symptoms make early diagnosis difficult. The mainstay of treatment is surgery in non-metastasised disease. Somatostatin analogues and peptide-related radionucleotide therapy (PRRT) are first-line medical therapy in well-differentiated tumours, but in our case, due to the poorly differentiated nature of the tumour, Metyrapone and chemotherapy were the preferred treatment options. The prognosis is guarded.