Case1. A 63-year-old woman with resistant hypertension and osteoporotic crush fractures was confirmed to have marked hypercortisolism with raised ACTH(31.3pmol/L). Repeated high-dose dexamethasone suppression tests failed to suppress cortisol. Brain MRI was inconclusive reporting possible pituitary microadenoma.
IPSS with CRH stimulation localised a central source of ACTH production to the Left(Figure1). Despite two transphenoidal hypophysectomy on two occasions she had persistent postoperative hypercortisolaemia unresponsive to ketoconazole therapy. Histopathology showed normal pituitary tissue(Figure2-A) with an incidental finding of a sphenoid mycetoma with aspergillus species.
Subsequently she was discovered to have bilateral pulmonary lesions and possible liver lesions on CT/MRI. FDG-PET and Ga68-Octreotide-PET were performed: both upper lobe lung lesions demonstrated FDG-avidity but no uptake on the Ga68-Octrotide scan(Figure3-A/B/C). She underwent pulmonary core biopsy twice(initial biopsy non-diagnostic) with normal/non-malignant histopathology(Figure2-B). Repeat lung biopsy and bronchoscopic lavage culture both yielded Nocardia asteroids, for which she was successfully treated with Bactrim(sulfamethoxazole-trimethoprim).
Due to persistent symptomatic hypercortisolaemia unresponsive to adrenal blockade with high-dose ketaconazole, the patient underwent emergency bilateral adrenalectomy with successful recovery.
Figure1
Figure2-A/B
Figure3-A/B/C
Case2. A 64-year-old Caucasian male presented with erratic glycemic control with recurrent psychosis, hypokalemia, hypertension and lymphopenia. Further investigations detected cavitating lung and multiple liver lesions. PET scan showed FDG uptake in the above lesions and also in the head of pancreas and pylorus. He underwent fine need aspiration of the lung lesion and Nocardia asteroids were found.
Core biopsy of the liver lesion revealed intermediate-grade neuroendocrine tumour with ACTH-positive stain. The 24-hour urine cortisol excretion was elevated, so was serum ACTH(86.1pmol/L). He was started on ketoconazole/metyrapone and palliative chemotherapy.
Discussion: These two cases illustrate complex presentation of ectopic ACTH syndrome with a serial of diagnostic and management challenges, including severe immunosuppressive complications. We will present literature review on data of relevant results, investigational modality and currently available therapy.