Endocrine Abstracts

Background: Diagnostic work-up for Cushing Syndrome (CS) can be challenging and is based on clinical and biochemical assessments. Biochemical evidence of endogenous steroid excess is demonstrated through overnight dexamethasone suppression test (ODST), low dose dexamethasone suppression test and/or 24-hour urinary free cortisol estimation (UFC). Once endogenous steroid excess is confirmed, random serum ACTH measurement is key in determining the suspected source of steroid excess: ACTH-independent (adrenal cause) or ACTH-dependent Cushing (pituitary or ectopic ACTH secretion). We report a case of CS where the serum ACTH caused diagnostic confusion during work-up for an adrenal incidentaloma.

Case report: A 42-year-old female was referred with a 2.6 cm left adrenal adenoma, discovered on CTPA when she presented with bilateral massive pulmonary embolisms necessitating thrombolysis. She had a history of anxiety and was newly diagnosed with type 2 diabetes. Her BMI was 38 kg/cm2 and she displayed Cushingoid features on clinical examination. Random serum ACTH levels ranged from 5 to 23 ng/l(NR <63). She failed her Overnight Dexamethasone Suppression Test and Low Dose Dexamethasone Suppression Test with a post-dexamathesone serum cortisol level of 69 nmol/land 75nmol/lrespectively. Her 24-hr UFC was normal. She had a blunted ACTH (ranging from 6 to 11 ng/l) and cortisol (ranging from 234 to 399 nmol/l) response on peripheral desmopressin test (IV desmopressin 10µg). Her pituitary MRI did not reveal any lesion and the right adrenal gland on her CT appeared normal. Given the diagnostic biochemical uncertainty on whether she has ACTH dependent or independent hypercortisolaemia, the patient agreed to a pragmatic suggestion to undergo unilateral left adrenalectomy in the first instance, with the caveat that hypercortisolaemia may persist post operatively. On day 2 post-adrenalectomy she passed her Synacthen test with a peak serum cortisol of 522 nmol/l. Subsequent assessment of her steroid dynamics did not reveal any steroid excess and the histology of the resected adrenal gland demonstrated an adenoma with atrophy of zona fasciculata.

Conclusion: Variable serum ACTH levels can cause diagnostic confusion in some cases of CS, especially in cases of cyclical Cushing’s. A robust clinical work-up, encompassing investigations for both pituitary and adrenal source of steroid excess, and a multi-disciplinary approach to interpretation of diagnostic tests and imaging is thus indicated in such cases.