Background: Lutetium 177 (177Lu) - DOTATATE is a form of peptide receptor radionuclide therapy (PRRT) utilized in the treatment of neuroendocrine tumours. Carcinoid and catecholaminergic crises have been previously described following PRRT. There have been no previous reports on 177Lu-DOTATATE-induced Cushing’s syndrome.
Case Description: A 55-year-old female with asymptomatic, well-differentiated, Grade 3 metastatic pancreatic neuroendocrine tumour previously treated with lanreotide and carboplatin/etoposide underwent first cycle PRRT with 177Lu-DOTATATE. Five days thereafter, she presented to hospital with rapid Early morning cortisol was elevated 1042nmol/L (185 – 624nmol/L), as was ACTH 411ng/L (7.2 – 63ng/L) and 24hour urinary free cortisol 9834nmol/day (60-305nmol/day). Cortisol did not suppress on 1mg dexamethasone suppression test (DST) at 1209nmol/L or on 8mg DST (cortisol 1444nmol/L; ACTH 462ng/L). Subsequent repeat 24hour urinary free cortisol five days following the initial revealed further elevation at 16,237nmol/day (60-305nmol/day). She was also hypokalaemic 2.9mmol/L (3.5-5.2mmol/L). Pre-PRRT serum potassium was repeatedly normal but cortisol and or ACTH were not measured. The patient was diagnosed with ectopic ACTH-dependent Cushing’s syndrome and was commenced on metyrapone and octreotide therapy leading to rapid reduction in plasma cortisol and ACTH levels. Retrospective immunohistochemistry of a liver metastasis revealed ACTH staining.
Summary: We report, for the first time, a patient with asymptomatic apparently non-functioning pancreatic neuroendocrine tumour, who rapidly developed symptomatic ectopic ACTH-dependent Cushing’s syndrome after 177Lu-DOTATATE therapy.
Conclusions: This case raises the possibility that akin to other hormonal crises, PRRT can trigger marked ACTH release from neuroendocrine tumour tissue, rapidly leading to clinical manifestations of Cushing’s syndrome. Whether the rapid improvement in ACTH and cortisol post PRRT was due to medical therapy, and/or due to offset of PRRT-associated ‘tumour lysis’ remains uncertain.