MON-412 Subclinical Cushing's Disease and the Importance of Broad Differential Diagnoses

Introduction: Cushing disease is the most common cause of endogenous Cushing syndrome, and if undiagnosed, carries significant morbidity including diabetes, obesity, infertility, and osteoporosis. Physical exam findings commonly seen include violaceous abdominal striae, supraclavicular fat pads, facial plethora, and proximal muscle weakness. Here, we discuss a case of a rare presentation of Cushing disease in a patient whose chief complaint was fatigue with none of the aforementioned physical manifestations. Case: A 43 year old female with a medical history of multinodular goiter status post hemithyroidectomy presented with persistent fatigue and weight gain over a one year period. Physical exam revealed normal body habitus, no thyroid nodules, no supraclavicular fat pad, abdominal striae, or proximal muscle weakness. Thyroid studies were normal, and despite lifestyle modifications, the patient's symptoms persisted. Laboratory workup revealed elevated midnight salivary cortisol levels, an elevated 24 hour urine free cortisol measurement, and on dexamethasone suppression testing, elevated ACTH levels, confirming Cushing disease. Pituitary MRI was significant for pituitary macroadenoma with cystic changes measuring 1.1x1.9cm and mild compression of the optic chiasm. The patient was transferred for surgical resection, where pathology was consistent with an ACTH-secreting adenoma. Discussion: Subclinical Cushing's disease is defined by an adrenocorticotrophic hormone (ACTH)-induced mild hypercortisolism without typical features of Cushing's disease. In a 2016 cohort study, the prevalence of subclinical and silent corticotroph adenomas was approximately 40%, making it imperative for practitioners to have a broad differential when evaluating patients with non-specific complaints. Additional studies show that clinically silent adenomas (adenomas with normal cortisol secretion and ACTH-immunopositive staining without autonomous ACTH secretion) have the risk of progressing to Cushing's disease, thereby carrying the risk of increased morbidity secondary to the metabolic derangements due to hypercortisolism. Finally, should surgical resection be warranted, the size of the adenoma has been associated not only with the level of difficulty of surgical resection, but also with the risk of recurrence. Ultimately, it behooves the medical community to obtain detailed histories, conduct thorough physical, and maintain broad differentials of rare conditions to allow for better screening.