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 cases of ACTH-dependent CS where the serum ACTH level remains persistently low.

Case report: A 55-year-old female patient was referred with a 3 cm left adrenal adenoma, first discovered 8 years prior. She had type 2 diabetes, hypertension and a history of psychosis. Her other comorbidities included chronic obstructive lung disease, ischaemic heart disease, valvular heart disease, obstructive sleep apnoea and rheumatoid arthritis. She was on a number of regular medications including centrally acting agents for pain control and antipsychotic agents. She displayed Cushingoid features on examination and her random serum ACTH levels ranged between 7 and 17 ng/l(NR <42). She failed her overnight dexamethasone suppression test (ODST) with a serum cortisol level of 107 nmol/lpost-dexamethasone and her Low Dose Dexamethasone Suppression Test was also positive. Although her 24-hour urine free cortisol estimation was normal, her untimed urine steroid profile demonstrated relatively increased proportions of cortisol metabolites in the direction of Cushing’s. A peripheral desmopressin test (IV desmopressin 10 µg) was positive with an ACTH increase of 85% and a serum cortisol increase of 40%. Her pituitary MRI did not reveal a discrete adenoma. She underwent Inferior Petrosal Sinus Sampling which confirmed a pituitary source of ACTH excess (ACTH IPSS: peripheral >3). Given her adverse anaesthetic risk profile she is currently being managed on medical therapy with metyrapone and fluconazole therapy.

Conclusion: Diagnosis of ACTH dependent Cushing’s in patients presenting through the adrenal incidentaloma pathway can be challenging, especially in the presence of suppressed serum ACTH levels from centrally acting medications. The presence of Cushingoid features and radiological suggestion of a hyperplastic-looking contralateral adrenal gland should trigger investigations for ACTH-dependent CS in those with proven hypercortisolaemia. A multidisciplinary approach to investigation and interpretation is advised.