Background: Ectopic adrenocorticotropic hormone (ACTH) is an uncommon, but not rare presentation of Cushing’s syndrome. Distinguishing the cause of Cushing’s syndrome, once established, can be difficult. Clinicians should be suspicious of Ectopic ACTH syndrome as underlying Cushing’s syndrome in patients who have a history of malignancy.
Case: We present the case of a 73-year-old male who presented with several months of nausea, weight loss, and abdominal discomfort. Imaging demonstrated multiple hepatic lesion, left apical lung lesion and lymphadenopathy. Biopsy of liver lesion demonstrated immunohistochemistry staining consistent with neuroendocrine tumour. He underwent systemic chemotherapy for metastatic atypical carcinoid tumour of the lung. Following chemotherapy he developed rapid weight gain, despite stability of metastatic carcinoid disease on serial imaging. Examination findings were consistent with Cushing’s syndrome. Biochemistry demonstrated new onset of hypokalaemia, 1mg and 8mg dexamethasone suppression test demonstrated lack of suppression of early morning cortisol. He was commenced on metyropone for treatment of Cushing’s syndrome, likely ectopic ACTH. Ongoing concerns of lack of normalization in serum cortisol resulted in up-titration of metyrapone, as well as the addition of ketoconazole. Subsequent serum cortisol levels performed using a more specific immunoassay, at a different laboratory, demonstrated a decline in serum cortisol levels. More specific liquid chromatography-tandem mass spectrometry is being undertaken.
Discussion: Dose titration of adrenal enzyme blockade therapy continues to be largely based on serum cortisol levels. Metyropone inhibits 11ß-hydroxylation in the adrenal cortex, leading to reductions in cortisol and aldosterone, with associated increased levels of circulating precursor steroids. Several cortisol immunoassays are susceptible to positive interference, with cross-reactivity of circulating cortisol precursors. Clinical vigilance, knowledge of the specificity of cortisol assay utilized, as well as an awareness of possible cross-reactivity with steroid precursors is essential to guide treatment decisions in ectopic ACTH syndrome, to avoid erroneous clinical decisions being performed.