A 44-year-old man, with a history of smoking, hypertension and chronic obstructive airway disease was noted to have proximal myopathy, central adiposity, skin atrophy and bruising. He had recently commenced denosumab for multiple atraumatic rib fractures. Screening investigations identified a persistent leucocytosis (neutrophils 14.0x109/L, monocytes 2.0x109/L), mild PTH-independent hypercalcaemia (corrected calcium 2.82 mmol/L, PTH 1.4pmol/L), vitamin D deficiency (23 nmol/L) and elevated serum cortisol (2803 nmol/L) with hypokalaemia (2.5 mmol/L). An initial myeloma screen was unremarkable. ACTH-dependent Cushing’s syndrome was confirmed with a 1mg dexamethasone suppression test demonstrating elevated cortisol (1082 nmol/L) and ACTH (108 pg/ml). Metyrapone, colecalciferol and antihypertensive therapies were initiated. Petrosal venous sinus sampling was consistent with ectopic ACTH production; however, no focal lesion was identified, despite multimodal imaging (pituitary MRI, high-resolution CT chest, serial CT-chest-abdomen-pelvis, FDG-PET, DOTATE-PET). The patient underwent an uncomplicated bilateral adrenalectomy and commenced adrenal steroid replacement (hydrocortisone 10mg twice daily, fludrocortisone 100mcg daily). The development of osteonecrosis of the jaw necessitated denosumab cessation. Over the two years following adrenalectomy, the patient developed weight loss, worsening renal function and declining bone density. A repeat myeloma screen was positive (IgA paraprotein 20g/L, kappa/lambda free light chain ratio 2.21) and bone marrow biopsy demonstrated 70% plasma cells. Chemotherapy with bortezomib and dexamethasone has commenced.
ACTH-dependent Cushing’s syndrome arises from pituitary or neuroendocrine tumours, typically of the lung, thymus, pancreas or appendix (1). The interplay between Cushing's syndrome and multiple myeloma is unknown. As dexamethasone is a cornerstone of myeloma management, untreated Cushing’s syndrome may mask overt disease (2). It is possible that ACTH may also drive myeloma development, warranting further research. This case highlights difficulties in the diagnosis and management of ectopic ACTH syndrome and the importance of reevaluation in situations of unexplained clinical decline.