Endocrine Abstracts

Introduction: We present a case series of 3 patients managed in our centre over the last 2 years, with endogenous Cushing syndrome (CS) from three distinct causes. This series provides a great learning opportunity for a rare childhood phenomenon.

Case 1: A 10-year-old girl presented with a history of significant weight gain and osmotic symptoms. Examination confirmed cushingoid features and hypertension (HTN). Tests confirmed diabetes, elevated 24-hour urinary cortisol while the ACTH suppressed on Dexamethasone suppression test (DST), consistent with ACTH-independent CS. Imaging showed bulky adrenal glands without focal lesions, and genetic testing confirmed PRKAR1A mutation consistent with primary pigmented nodular adrenocortical disease (PPNAD). She was treated with metyrapone and anticoagulants, followed by bilateral adrenalectomy. Echocardiography excluded cardiac myxomas. Postoperatively, she has lost 20 kg of weight, and HTN and diabetes have resolved. She is stable on hydrocortisone (HC) and fludrocortisone (FCN) therapy.

Case 2: A 14-year-old girl presented with growth and puberty arrest and increasing fatigue. Clinically, she looked Cushingoid. Biochemistry showed elevated urine cortisol and a lack of ACTH suppression on DST, consistent with ACTH-dependent Cushing’s disease. MRI pituitary was inconclusive. She underwent inferior petrosal sinus sampling (IPSS) for localisation, which was also inconclusive. Management included metyrapone and anticoagulation, followed by exploratory pituitary surgery, which identified a lesion which was removed. She is now stable on HC replacement.

Case 3: A 15-year-old male presented with malaise, anxiety, and rapid weight gain. Examination revealed HTN, hyperglycaemia, and an abdominal mass. Tests showed elevated ACTH and cortisol levels. Imaging revealed widespread metastatic lesions, consistent with ACTH-producing neuroendocrine tumour, likely originating from the right lung. He was treated with chemotherapy and metyrapone; insulin and antihypertensives were briefly required. Denosumab was used for the metastatic bone lesions. Unfortunately, his condition progressed, and he sadly passed away one year later.

Conclusion: Childhood CS is rare. Weight gain and growth retardation are hallmark features of CS. Evaluation typically includes 24-hour urinary cortisol. DST is considered the gold standard for distinguishing between ACTH-dependent and independent CS. Whole-body imaging helps identify potential ACTH-secreting neuroendocrine tumours. Management is guided by the underlying aetiology, with metyrapone a beneficial adjuvant therapy.