Endocrine Abstracts

Background: Ectopic ACTH secretion leading to Cushing’s syndrome poses major diagnostic challenges, particularly when the source is obscured by co-existing pathology. Pulmonary cryptococcosis though uncommon, is an important infectious mimic of malignancy in immunocompromised states. Distinguishing infection-related nodules from an ACTH secreting lesion is essential, yet often delayed due to overlapping features.

Case report: A 47-year-old man with type 2 diabetes, hypertension and progressive Cushingoid features was found to have ACTH-dependent hypercortisolism (cortisol 700-800nmol/l, ACTH 632-156ng/l) with failure to suppress on overnight dexamethasone testing. Inferior petrosal sinus sampling confirmed ectopic ACTH secretion and metyrapone was commenced. Ga⁶⁸DOTATATE PET/CT demonstrated a cluster of left lower lobe nodules with low-level uptake. FDG-PET/CT prompted by neuroendocrine MDT, revealed 3-4 cavitating FDG-avid nodules. Biopsy showed dense inflammatory change consistent with fungal infection, and serology supported pulmonary cryptococcosis. Fluconazole was initiated, but subsequently symptomatic hypocortisolism occurred, likely due to a synergistic drug interaction, requiring block-and-replace therapy. Over subsequent months, lung parenchymal changes regressed and cryptococcal antigen titres fell from 1:32 to negative. However, interval CT revealed new soft tissue foci in the anterior mediastinum, prompting further MDT review. Follow-up imaging identified a distinct basal left lower lobe nodule that had enlarged with moderate DOTATATE uptake, in contrast to the regressing infection-related nodules. CT-guided biopsy confirmed a typical pulmonary carcinoid tumour (synaptophysin+, chromogranin+, CD56+), establishing the ACTH-secreting primary. Surgical resection planned.

Discussion: This case highlights diagnostic complexity of ectopic Cushing’s syndrome. Pulmonary cryptococcosis may obscure or mimic the radiological appearance and metabolic activity of an underlying neuroendocrine tumour. A coordinated multidisciplinary approach, supported by serial imaging and targeted histopathology was essential in establishing a pulmonary carcinoid tumour. Clinicians should retain a high index of suspicion for dual pathology in ectopic Cushing’s syndrome, as overlapping processes can substantially delay accurate localization and timely management.