SAT-LB52 A Case of Cushing’s Syndrome in a Patient With Addison’s Disease

This is a case of a 56-year-old female with history of Addison’s disease, T1DM, hypothyroidism and Asthma. She was diagnosed with Addison’s disease after multiple hospital visits consistent with adrenal crises (Fatigue, weakness, salt craving, abdominal pain, hypotension, hyperpigmentation and hyponatremia). Multiple abdominal images including CT abdomen did not reveal any pathology. A random cortisol and ACTH were found to be abnormal at 0.5 and 3362, respectively. She was started on Hydrocortisone 10mg in the morning and 5mg in the evening. Her physical exam revealed diffuse hyperpigmentation including palmar creases and oral mucosa. There was no facial plethora or striae. She had no history of proximal myopathy, easy bruising, hypertension or osteoporosis. Upon follow up, exam revealed progressive worsening of her diffuse hyperpigmentation. A random cortisol and ACTH, without holding her Hydrocortisone, revealed 64.3 and >2000, respectively. Concern arose for the possibility for a pituitary corticotrophin adenoma or ectopic secretion of ACTH driving her hyperpigmentation. MRI showed the pituitary gland had normal appearances. As there is a positive correlation between basal plasma ACTH values and the size of the pituitary adenoma in patients with Cushing’s disease the differential of a pituitary corticotrophin adenoma was originally thought to be dropped lower on the list of differentials. Further workup was pursued with an 8mg Dexamethasone suppression test to take advantage of the fact that ACTH secretion by the pituitary adenomas in Cushing’s disease are only relatively resistant to negative feedback regulation by glucocorticoids while most ectopic ACTH production from non-pituitary tumors are completely resistant to feedback inhibition. ACTH levels went from >2000 down to 29 post 8mg Dexamethasone, which led to decreasing suspicion of an ectopic source of ACTH and further concern for a pituitary corticotrophin adenoma in addition to Addison’s disease. ACTH measurements are not widely used in documenting the adequacy of treatment of primary adrenocortical disease. The hormone is released in pulses, particularly in the early hours of the morning, and measurement of isolated samples is of limited value. Inappropriately normal to slightly elevated ACTH levels despite adequate glucocorticoid replacement in patient with adrenal insufficiency could be related to an altered pituitary sensitivity to cortisol suppression. Extremely elevated ACTH levels despite supra-physiological glucocorticoid replacement in a patient with Addison’s raises the question as to what is the source of ACTH?