IMPE Abstracts

Cushing’s syndrome (CS) is a rare pediatric endocrine disorder. Most cases originate from pituitary lesions and less than 1% are caused by ectopic ACTH-secreting tumors. A previously healthy 9-year-old girl developed abrupt weight gain, Cushingoid phenotype, and behavior changes over 5 months. Subsequently, she developed fever, diarrhea, abdominal pain, abnormal gait, and myalgia. She was admitted to a local hospital with symptomatic hypokalemia requiring IV potassium correction followed by clinical deterioration, hypertension, and neurological symptoms requiring mechanical ventilation for 6 days. Complications included impaired kidney function, pericarditis, and seizures (CT scan showed posterior reversible encephalopathy syndrome), bacteremia, parasitosis, myositis, and cytosteatonecrosis of the thighs. CS was suspected and ACTH-dependent hypercortisolism was biochemically confirmed. Brain MRI showed no pituitary lesion. Ketoconazole treatment was initiated. At our institution, we confirmed the CS phenotype, Tanner Stage 1, advanced bone age of 1.5y, weight 97^th percentile (pc), height 75^th pc, blood pressure (BP) 95^th pc, and normal potassium levels with diuretics. Impaired plasma glucose with an altered oral glucose tolerance test (OGTT) and osteomyelitis were found. Ketoconazole was withdrawn and hypercortisolism verified: urinary free cortisol (UFC) >1641 mg/day and ACTH 170 pg/ml. An ectopic tumor was suspected after lack of inhibition with 8 mg dexamethasone and petrosal sinus catheterization without a central/peripheral gradient. Abdominal and pelvic MRI detected no tumor, but chest MRI showed a doubtful mediastinal lesion. Ga-Dotatate PET/CT scan confirmed this finding. Histological evaluation of the removed tumor showed positive markers for ACTH, enolase, chromogranin, synaptophysin, CKAE1/AE3, mitosis, focal necrosis and a Ki67 of 3%. An atypical thymic carcinoid tumor was diagnosed. Postsurgical studies evidenced indetectable UFC, cortisol inhibition with 1 mg dexamethasone, and night cortisol <1 mg/dl. Three months later, Ga-Dotatate PET/CT scan showed no tumor uptake. Nineteen months after the procedure, there was no evidence of biochemical hypercortisolism, nor any pathological uptake in the Ga-Dotatate PET/CT scans. The patient lost weight and BMI normalized and linear growth continued. She had spontaneous puberty with menarche at 10.6y and last height measurement was149.7 cm. There was an improvement in BP, muscle strength, and glucose metabolism and fasting plasma glucose and OGTT normalized.

Conclusion: Neuroendocrine tumors should be considered in patients with a Cushingoid phenotype, ACTH-dependent hypercortisolism, and absence of a pituitary lesion. Prompt diagnosis is important as they are associated with high morbidity and mortality, and surgery is the only curative treatment.