A 69 year old man presented with behavioural changes and memory deficits. His past medical history included obesity, ischaemic heart disease, hypertension and dyslipidaemia. He was an ex-smoker who did not drink alcohol. MRI revealed 2cm pituitary macroadenoma extending upwards towards the optic chiasm. Baseline electrolytes and liver function were in the normal range. Further pituitary screening demonstrated hypogonadotropic hypogonadism, reduced fT3 with normal fT4, normal prolactin and fasting glucose levels, plus elevated ACTH 24 pmol/L (<11) with high early morning cortisol 976 nmol/L (120-620). Visual field testing was consistent with incomplete superior bitemporal quadrantanopia. 24-hour urinary free cortisol of 7747 nmol/day (54-319) combined with failure of cortisol suppression after 1mg overnight dexamethasone confirmed Cushing’s syndrome.
Two weeks later he was suffering orthopnoea and 10kg rapid weight gain; he was admitted for management of oedema and determination of ACTH hypersecretion source. Following low-dose DST peak cortisol and ACTH were measured at 2412 nmol/L and 50.6 pmol/L respectively. High dose DST was abandoned due to discovery of markedly impaired liver function with multiple liver and lung metastases, severe haematuria requiring transfusion and septic shock requiring vasopressor support. Ketoconazole therapy was not pursued due to impaired liver function. On Day 7 liver biopsy revealed small cell neuroendocrine carcinoma, likely non-small cell lung primary. On Day 9 chemotherapy (CHOP) was commenced with a drop in cortisol level to 198 nmol/L noted by Day 14. Despite supportive management he passed away on Day 20 with complications of febrile neutropenia. Eventual staining of the liver specimen was mildly positive for ACTH.
Conclusion: This case demonstrates the clinical challenges in pursuing a diagnostic approach for pituitary marcoadenoma when unrecognised ectopic ACTH secretion is the likely source. Prognosis in such cases is poor, although rapid resolution of hypercortisolaemia suggest prompt diagnosis and institution of chemotherapy is indicated for symptom relief.